The most frequent driver mutations implicated in HCC progression affect telomerase reverse transcriptase (TERT) gene with promoter mutations in 60% of cases, WNT-β-catenin pathway with mutation in the CTNNB1 gene ranging from 11% to 37% and are responsible for the inactivation of both the TP53 gene (10%–30%) and the cell cycle regulator gene CDKN2A (2%–12%) [4]. The gene discussed is TP53; the disease is hepatocellular carcinoma.