A cohort of 67,909 participants, followed from 2012 to 2021, was used to evaluate the long-term HCC risk associated with these variants.<h4>Results</h4>Ten SNPs in <i>PNPLA3/SAMM50</i> were significantly associated with HCC risk (<i>p</i> <1.62 × 10<sup>-7</sup>) and were in high linkage disequilibrium. Here, PNPLA3 is linked to hepatocellular carcinoma.