We observed that (1) MBOAT7 rs641738 is independently associated with inflammation and the transition to early fibrosis; (2) hepatic MBOAT7 expression correlates with inflammation; (3) rs641738 genotype has no association with the severity of hepatic steatosis, HCC occurrence; (4) rs641738 genotype associates with MBOAT7 transcript and protein expression in liver and blood in opposite directions, and with serum inflammatory, oxidative stress and macrophage activation markers; and (5) MBOAT7 is well expressed by all major immune cell subsets. Here, MBOAT7 is linked to hepatocellular carcinoma.