In cirrhotic HCC, the ER group with hypermethylation exhibits the top 10 prominent pathways, which encompass the activation of HOX genes, defective p16INK4A binding to CDK4 and CDK6, FOXO-mediated transcription of cell death genes, TP53 regulated transcription, G protein-gated potassium channels, extracellular matrix organization, adherent junction interactions, and the aberrant regulation of the mitotic cell cycle due to RB1 defects. This evidence concerns the gene RB1 and hepatocellular carcinoma.