Kim Ji-hoon began his entertainment career as a video jockey in 2001. He then made his acting debut in the 2002 KBS2 series Loving You. In 2006, he appeared in the MBC drama How Much Love, in which he was nominated for Best New Actor at the MBC Drama Awards. The following year, he was named Best New Actor at the KBS Drama Awards for his work in Golden Age for Daughters-in-Law. He also took home the Best Couple Award with Lee Soo-kyung for the said series. In 2010, he landed his first film role in Natalie, which is the first Korean 3D mellow movie. In 2013, he picked up an Excellence Award at the SBS Drama Awards for the romantic comedy drama Goddess of Marriage. In 2014, he joined the cast of the MBC series Jang Bori Is Here, which won him two Top Excellence Awards. In 2018, he was nominated for a Top Excellence Award at the MBC Drama Awards for his starring role in the family drama Wealthy Son. In 2020, he played the role of a psychopath killer in the tvN series Flower of Evil. His performance in the drama earned him a Best Supporting Actor nomination at the 57th Baeksang Arts Awards.

Kim Ji-hoon entered the military for his mandatory service on October 4, 2010. He was discharged on July 11, 2012.