Mechanistically, constitutive methylated RIG-I at K18 and K146 enhances hepatic cholesterol synthesis and lipid accumulation, thus promoting steatosis and the following NASH and NASH-HCC, whereas JMJD4-demethylated RIG-I suppresses IL-6 response and inflammation-induced hepatocarcinogenesis. Here, JMJD4 is linked to hepatocellular carcinoma.