This study aimed to evaluate the impact of the genetic polymorphisms PNPLA3 rs738409, TM6SF2 rs58542926, and HSD7B13 rs6834314 on susceptibility to hepatocellular carcinoma (HCC) in a cohort of HCC patients with two different etiologies: MASLD-HCC and VIRAL-HCC, as well as to determine whether these genetic variations correlated with the prognosis of HCC. Here, PNPLA3 is linked to hepatocellular carcinoma.