This review dissected recent findings on the role of several lipid droplet-associated factors, patatin-like phospholipase domain-containing 3 (PNPLA3), Transmembrane 6 superfamily member 2 (TM6SF2), and 17β-hydroxysteroid dehydrogenase (HSD17B) 11 and 13 as well as their genetic variations in hepatopancreatobiliary diseases, especially cancer. The gene discussed is PNPLA3; the disease is cancer.