To gain further insight into the role of cholesterol ester accumulation in hepatocarcinogenesis, several cholesterol biosynthetic enzymes were targeted and it was found that the sterol O-acyltransferase 1 (SOAT1) inhibitor avasimibe inhibited HCHFD-induced HCC induction and cholesterol ester synthesis in a p53-independent manner. Here, SOAT1 is linked to hepatocellular carcinoma.