In four out of five training and validation datasets with available clinicopathological factors, HCCEvoSig was significantly associated with OS in multivariate Cox proportional hazards analysis, adjusting for age, sex, TNM stage, histological grade, cirrhosis, and AFP (Supplementary Table S11-15, TCGA-LIHC: p = 0.0008, HR = 3.11 [1.60–6.06]; ICGC-LIRI-JP: p = 0.0031, HR = 3.71 [1.56–8.86]; CHCC-HBV: p = 0.0002, HR = 3.45 [1.82–6.55]; and FULCI-HCC: p = 0.0038, HR = 2.05 [1.26–3.34]). This evidence concerns the gene AFP and Cirrhosis.