We aimed to evaluate the performance of a PRS, including variants in PNPLA3 (patatin-like phospholipase domain containing 3), MBOAT7 (membrane bound O-acyltransferase domain containing 7), TM6SF2 (transmembrane 6 superfamily member 2), and GCKR (glucokinase regulator), for predicting risk of developing HCC in two contemporary U.S-based multiethnic cohorts of patients with cirrhosis. The gene discussed is TM6SF2; the disease is hepatocellular carcinoma.