However, few studies have investigated genes that are repressed in fetal hepatocytes, activated in the adult liver, but re‐silenced in HCC, which we define as “oncofetal suppressors.” In the present study, we identified ESRP2 as a novel oncofetal suppressor that inhibits HCC proliferation and migration by promoting the fetal‐to‐adult switch in RNA‐splicing programs. This evidence concerns the gene ESRP2 and hepatocellular carcinoma.