In 1999, Yang made her acting debut by playing Zhou Qiong in Ru Ci Chu Shan. In 2002, Yang had a minor role as little Consort Donggo in Xiaozhuang Epic. In May 2004, Yang made her big-screen debut in the youth romance film Girl's Diary, playing Ran Dongyang, an elementary school student. She received a Best Child Actor nomination at the Tongniu Film Awards for her performance in the film.

In 2005, Yang rose to prominence playing Xia Xue in the popular Mainland Chinese sitcom Home with Kids. The series reached number one in ratings when it aired in China, and won the Outstanding Television Series (for children) award at the Flying Apsaras Awards and the Golden Eagle Awards. Yang became a household name in China since then. In March, she played little Bing Yue in historical costume drama Young Kangxi. In 2006, she reprised her role as Xia Xue in the sequel Home with Kids 2, though not in the subsequent installments.
In June 2008, Yang released her first solo album titled Home with Snow, which is named after her character's name in Home with Kids. In 2009, Yang voiced Ma Xiaotiao in the comedy animation series Mo's Mischief: Teacher's Pet, adapted from Yang Hongying's children's literature series of the same name. The same year, Yang played her first leading role in the youth drama Girl Rushes Forward.

In 2010, Yang starred in the friendship drama Boy's Diary. Then she was admitted to the Performance Institute of Beijing Film Academy. In February 2011, she starred in the family drama Love Comes Knocking on the Door, based on the novel Stepmother by Geling Yan. Her role as a rebellious teenager allowed her to successfully shed her image of a "child star".

In May 2012, Yang starred in the medical drama Angel Heart, portraying a kindhearted nurse. In August, she starred in the horror mystery thriller film Insisrence, and won the Best Newcomer Award at the 14th Golden Phoenix Awards. She also performed the official soundtrack, "The Quiet Rubble" for the film. In February 2013, Yang played the lead role in the period comedy drama King Rouge. In April, she starred in the family drama Dad Comes Home. In August, she starred in the romance drama Flowers in Fog, written by acclaimed Taiwanese writer Chiung Yao.
In March 2014, Yang starred in her first war drama Battle of Changsha, directed by Magnolia Award-winner Kong Sheng. The show was set against the backdrop of the Battle of Changsha in 1939 during World War II. Yang played the role of Hu Xiangxiang, a nurse in the field hospital with different temperaments from the bright and lively girlhood to the aftermath of being a wife and a mother. The show was a critical success and was voted Best Drama of 2014 in major streaming website Douban after being broadcast on CCTV-8 beginning mid-July 2014. In May, Yang joined the second season of youth inspirational reality show We Are Young as a regular cast member.

In April 2015, Yang joined Dragon TV's star travel-reality show Sisters Over Flowers as a regular cast member. In August, she starred in the youth romance film Where Are All The Time. In October, Yang starred in the period drama Yangko Dance, which is a story inspired by the Haiyang Yangge folk dance tha…

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Yang has become one of China's most in demand brand ambassador due to her nationwide popularity. She endorses a wide range of products including food and beverages, daily necessities and hygiene products, fashion and beauty, mobile applications and games etc. She endorses many well-known international brands including Valentino, Prada Beauty, APM Monaco, and Michael Kors, as well as big domestic brands such as Bosideng, Yang Yuan Qing and BOLON Eyewear. In August 2022, Chery Automobile announced Yang as their global brand ambassador.

On 3 July 2023, Yang was appointed as the official ambassador for MLB China. She attended the MLB All Star Game in Seattle on 11 July. In October 2023, she attended the Valentino Paris Fashion Week show and was subsequently announced as Valentino's Brand Ambassador the month after. APM Monaco announced Yang as their Global Brand Ambassador in December 2023 and in April the following year, she launched her own Capsule Collection with the brand. In January 2024, Yang was announced as Prada's Makeup and Fragrance Ambassador. In September 2024, she took on the title of Michael Kors APAC Brand Ambassador.
On 27 January 2017, Yang appeared on the stage of CCTV Spring Festival Gala for the first time and performed the opening song "Beautiful Youths of China" with her sisters from Ode to Joy and TFBoys. On 16 September, she appeared on Vision Wei's 10th Anniversary Concert in Beijing as a special guest, performing "Looking for Someone" and "Our Little World" with the singer. On 15 February 2018, she participated in the comedy skit "At Your Service" at the CCTV Spring Festival Gala with Lin Yongjian, Li Mingqi and Dai Chunrong. On 31 December, she attended the Hunan TV New Year Eve Concert and performed the song "Unsullied" which is the opening theme song of her drama Ashes of Love.

On 4 February 2019, Yang participated in the comedy skit "Platform" at the CCTV Spring Festival Gala with Shang Daqing, Li Wenqi, Huang Xiaojun and Tong Dawei. On 5 February, she appeared on the Beijing Television Spring Festival Gala and sang the song "Childhood" with 3 other artist. On 31 December, she participated in the Hunan TV New Year Eve Concert, performing "Possible Night". On 24 January 2020, she performed "Meeting in 20 Years Again" alongside Angela Zhang, Xu Ziwei and Roy Wang at the CCTV Spring Festival Gala. On 25 January, she participated in Beijing Television Spring Festival Gala together with her co-stars from Home with Kids and performed the song "Beijing, My Love". She was named the promotional ambassador for the event in December 2019. On 30 September, she participated in the 2020 CCTV National Day Gala and sang the song "Upward Light". On 17 October, Yang attended the 70th Anniversary Celebration of Beijing Film Academy and presented the opening speech of the ceremony. On 31 December, she participated in the Dragon TV New Year Eve Concert, performing "Unsullied", "One person Likes One Person", "Milk Bread" and "Us", the OST of her drama Ashes of Love, The Oath of Love, Go Go Squid! and Ode to Joy respectively.

On 4 May 2021, she participated in CCTV's May 4 Youth Day special program "Fight for Youth" and performed the song "Landscape Painting". On 31 Dece…

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Due to the popularity of Home with Kids, Yang was dubbed as the "Nation's Daughter". In September 2016, she was picked as one of the Four Dan Actresses of the post-90s generation by a survey conducted Southern Metropolis Daily among 173 million netizens and 110 professional media and industry insiders. She ranked 73rd on Forbes China Celebrity 100 list in 2017. Forbes China also listed her under their 30 Under 30 Asia 2017 list which consisted of 30 influential people under 30 years old who have had a substantial effect in their respective fields.

In July 2019, after Go Go Squid! became a massive hit, iQiyi awarded Yang a KPI锦鲤 pennant. Her digital cover of Esquire Fine China September issue sold more than 150K copies in 10 minutes. In December, she was awarded the "iQiyi Scream Goddess" award at the 8th iQiyi All-Star Carnival. She ranked 24th on Forbes China Celebrity 100 list in 2019 and 13th in 2020. In January 2020, The Beijing News selected her as the 2019 Entertainment Person of the Year. She was awarded Weibo Queen at the Weibo Awards Ceremony. On May, she was named the Most Influential Actress of 2019 by Powerstar China. She appeared on the Forbes Asia's 100 Digital Star list, comprising 100 artists from across the Asia-Pacific region who have been able to stay active, raise awareness and inspire optimism despite the cancellation of physical events during the COVID-19 pandemic. Weibo Entertainment announced Yang as the "Most Commercially Valuable Star" of 2020.

In 2021, Yang ranked 8th on Forbes China Celebrity 100. She was awarded Weibo Queen again at the Weibo Awards Ceremony. In 2023, she became the first post-90s actress to take the cover of first line men's magazine Esquire China. She also became the first ever female to have the dual cover issue for Esquire China and Esquire Fine China. The December issue of Cosmopolitan China with Yang as the cover star sold 100K copies in less than 1 hour and more than 180K copies in first 24 hours.

In January 2024, she was awarded Weibo Queen for the third time, which makes her the only actress to win this honor thrice. She was named "Actress of the Year 2023" by the Chinese magazine People (人物) and appeared on the cover of the magazine as one of the Faces of the Year. Yang was chosen as the "Most Likeable Celebrity" by 70 media professionals by a survey conducted by Sohu Entertainment. In June 2024, she was announced as one of the torchbearers for the Paris 2024 Olympics.

As of December 2023, Yang has more than 60 million followers on Chinese microblogging platform Weibo. Her topic on Douyin has exceeded 150 billion views making her the first and only post-90s actress to do so.
Yang has been a WildAid Ambassador in China since 2019. On 20 December 2019, Yang participated in "Green Lifestyle" charity project jointly created by China Youth Daily, China Youth Online and WildAid and served as the Green Lifestyle Public Welfare Promotion Ambassador. In November 2020, Yang was announced as the Promotional Charity Ambassador of WildAid, advocating to protect wildlife. On 30 April 2021, WildAid and the China Wildlife Conservation Association co-launched a new PSA and billboard entitled "Bring Home Memories, Not Regrets" in China. The new campaign, led by Yang, calls on f…

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