There was a significant association between PNPLA3 148M homozygosity and higher HCC grade in patients with ALD&NAFLD (10/12, 83% vs. 10/22, 45%; p = 0.03), but not in those with other liver diseases (7/10, 70% vs. 40/74, 54%; p = 0.3). Here, PNPLA3 is linked to metabolic dysfunction-associated steatotic liver disease.