Professionally trained in ballet at the Beijing Dance Academy, Liu Shishi made her acting debut in a leading role in the television drama series The Moon and the Wind (2005), which included a specially designed segment of Swan Lake.

[4][5][6] In 2010, Liu starred in the historical drama A Weaver on the Horizon, based on the life story of Huang Daopo.

[7] In 2011, Liu starred alongside Wallace Huo in period action drama The Vigilantes In Masks, which received positive reviews.

[13] In 2012, Liu starred in action drama Xuan-Yuan Sword: Scar of Sky, adapted from the video game of the same name.

[26] In 2016, Liu headlined the historical drama The Imperial Doctress, based on the life of Tan Yunxian, a female physician during China's Ming Dynasty.

[28] In 2017, Liu starred along actors Wang Qianyuan and Cao Bingkun in the spy drama The Battle at Dawn.

[30] Liu then starred in historical fantasy drama Lost Love in Times alongside William Chan,[31] as well as the crime suspense film The Liquidator where she played a palaeoichnology expert.

[36] Liu married her Scarlet Heart co-star Nicky Wu on January 20, 2015[37] and their wedding ceremony was held in Bali, Indonesia on March 20, 2016.