Lee Ji-hoon debuted as an actor in the 2012 KBS2 teen series School 2013. The following year, he played supporting roles in KBS2’s You’re the Best, Lee Soon-shin and MBC’s Golden Rainbow. His performance in the former earned him a Best New Actor nomination at the KBS Drama Awards. In 2016, he received a Special Acting Award nomination at the SBS Drama Awards for his villainous role in the fantasy romantic comedy Legend of the Blue Sea. In 2019, he became part of the MBC sageuk Rookie Historian Gu Hae-ryung, which won him Best Supporting Actor at the MBC Drama Awards. In 2020, he acted alongside Song Seung-heon and Seo Ji-hye in the MBC romance series Will You Have Dinner With Me, in which he was nominated for an Excellence Award at the MBC Drama Awards.

Lee Ji-hoon attended Hallym University.