GOALS: To elucidate whether long-term supplementation with branched-chain amino acid (BCAA) granules improves overall survival (OS) and recurrence-free survival (RFS) after radiofrequency thermal ablation (RFA) in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)≤3 cm in diameter with up to 3 nodules and a serum albumin level before RFA of ≤3.5 g/dL. BACKGROUND: Whether BCAA treatment after curative RFA for patients with HCV-related HCC improves OS and RFS remains unclear. STUDY: We compared the OS rate and the RFS rate between the BCAA group (n=115) and the control group (n=141). We also examined factors contributing to OS and RFS. RESULTS: The 1 and 3 years OS rates after RFA were 94.0% and 70.0%, respectively, in the BCAA group, and 94.0% and 49.8%, respectively, in the control group (P=0.001). The corresponding RFS rates 1 and 3 years after RFA were 61.8% and 28.0%, respectively, in the BCAA group, and 52.0% and 12.0%, respectively, in the control group (P=0.013). In the multivariate analysis, in terms of OS, BCAA treatment, and serum albumin level of ≥3.4 g/dL, and in terms of RFS, age 70 years or older, BCAA treatment, and a serum albumin level of ≥3.4 g/dL were significant independent factors, respectively. CONCLUSIONS: BCAA treatment may improve OS and RFS after RFA in patients with HCV-related HCC≤3 cm in diameter with up to 3 nodules and a serum albumin level before RFA of 3.5 g/dL.