These findings highlight their potential utility as biomarkers for HCC risk stratification and underscore the need for further research into underlying mechanisms.<h4>Impact and implications</h4>Variants in the <i>PNPLA3/SAMM50</i> locus were significantly associated with hepatocellular carcinoma (HCC) risk in individuals seronegative for HBsAg and anti-HCV. Here, SAMM50 is linked to hepatocellular carcinoma.