In this unicentric prospective study, we analyzed the most prevalent mutations in HCC (TERT promoter, TP53, CTNNB1, AXIN1 and ARID1A) in plasma cfDNA by next-generation sequencing, aiming to elucidate their value as prognostic noninvasive biomarkers. The gene discussed is CTNNB1; the disease is hepatocellular carcinoma.