Han Ji-hye began her entertainment career as a model before she took on supporting roles in television dramas. She landed her first leading role in the KBS2 drama Sweet 18 in 2004. Her performance in the series won her Best New Actress for TV at the 40th Baeksang Arts Awards. In 2005, she scored back-to-back Best New Actress nominations at the 42nd Grand Bell Awards and the 26th Blue Dragon Film Awards for the movie My Boyfriend Is Type B. In 2007, Han Ji-hye starred in the hit daily series Likeable or Not, which earned her two Excellence Award trophies. In 2008, she was cast in the epic drama East of Eden, in which she received an Excellence Award at the MBC Drama Awards. In 2012, she won two Top Excellence Awards for her leading role in the MBC drama May Queen. In 2014, she became a part of the MBC weekend series Legendary Witch, which recorded a peak viewership rating of 31.4 percent.

In 2008, Han Ji-hye recorded the Korean version of the Beijing Olympics swimming theme song titled Friends. She also released the digital single Luv Luv featuring Soul Tronik in 2009. That same year, Han Ji-hye designed and produced her own shoe collection in partnership with designer Jinny Kim. In 2010, she published the book My Fair Lady, featuring a collection of lifestyle essays she wrote herself.

Han Ji-hye married public prosecutor Jung Hyuk-joon in a private ceremony in Hawaii on September 21, 2010. She gave birth to their first daughter on June 23, 2021.