Choi Kang-hee, born Choi Se-yun, made her acting debut in the 1995 KBS1 high school drama The New Generation Report: Adults Don’t know. She then appeared in the first installments of the 1998 horror film Whispering Corridors and the 1999 KBS teen drama School. In 2006, Choi Kang-hee was cast in the sleeper hit movie My Scary Girl, in which she was nominated for Best Actress at the 27th Blue Dragon Film Awards. She then headlined the 2009 comedy drama film Goodbye Mom together with Kim Young-ae. She took home the Most Popular Actress trophy at the 46th Baeksang Arts Awards and the Popular Star Award at the 30th Blue Dragon Film Awards for her work in the movie. In 2011, she won another Popular Star Award at the 32nd Blue Dragon Film Awards for the 18-rated romantic comedy film Petty Romance. That same year, Choi Kang-hee won a Top Excellence Award at the SBS Drama Awards for the workplace romantic comedy Protect the Boss. She then took on the lead role in the first and second seasons of the KBS2 detective comedy Mystery Queen from 2017 to 2018.

Aside from acting, Choi Kang-hee is also a radio DJ. In 2006, she was named Best Radio Host at the 13th Korean Entertainment Awards for Pump up the Volume. She also pursued other endeavours such as writing. In 2009, the actress released a photo essay book, which contained poems and essays she wrote herself as well as photos she took from a trip to Iceland. She donated all the profits from her book to charity.

In 2013, Choi Kang-hee revealed during a show guesting that she previously dated two co-stars. When asked who the actors are, the actress refused to reveal their identities.