In allelic models, carriers of the risk allele had higher HCC risk, with adjusted hazard ratios (95% CI) of 1.88 (1.14-3.10) for rs738409, 1.68 (1.02-2.78) for rs2281135, and 1.61 (0.98-2.67) for rs2235776.<h4>Conclusions</h4>This study identified <i>PNPLA3/SAMM50</i> variants significantly associated with long-term HCC risk in individuals without viral hepatitis. Here, PNPLA3 is linked to animal viral hepatitis.