This analysis showed that older age (OR = 1.12; 95% CI: 1.07–1.17; p < 0.0001), PNPLA3 genotype GG (OR = 2.62; 95% CI: 1.15–5.96; p = 0.0218), and male gender (OR = 1.83; 95% CI: 0.90–3.71; p = 0.0936) were factors independently associated with the development of HCC, although the association with gender was only a tendency. This evidence concerns the gene PNPLA3 and hepatocellular carcinoma.