4104 Background: Which is the best treatment for less advanced hepatocellular carcinoma (HCC) with good liver function remains one of the most important and unsolved problems. To solve this problem, we conducted this study and evaluated the therapeutic impacts of surgical resection (SUR), percutaneous ethanol injection (PEI), and radiofrequency ablation (RFA) on long-term outcomes in patients with HCC. Methods: A large-scale database constructed by a Japanese nationwide survey was used for this study. Between 2000 and 2005, 28,510 patients with HCC were treated by SUR, PEI, or RFA, among whom we identify 12,968 patients with no more than 3 tumors (≤3cm) and liver damage of class A or B. The patients were divided into SUR group (n=5,361), RFA group (n=5,548), and PEI group (n=2,059). Rates of overall and recurrence-free survival were compared among them. Results: Median follow-up was 2.16 years. Overall survival rates at 3 and 5 years were respectively 85.3%/71.1% in the SUR group, 81.0%/61.1% in the RFA, and 78.9%/56.3% in the PEI. Recurrence-free survival rates at 3 and 5 years were 56.7%/36.2%, 42.8%/28.3%, and 35.7%/23.1%, respectively. On multivariate analysis, the hazard ratio for death was significantly lower in the SUR group than in the RFA (SUR vs. RFA:0.84, 95% confidence interval, 0.74-0.95; p=0.006) and the PEI (SUR vs. PEI:0.75, 0.64-0.86; p=0.0001). The hazard ratios for recurrence were also lower in the SUR group than in the RFA (SUR vs. RFA:0.74, 0.68-0.79; p=0.0001) and the PEI (SUR vs. PEI:0.59, 0.54-0.65; p=0.0001). Conclusions: Surgical resection would provide longer overall and recurrence-free survival than either RFA or PEI in patients with HCC.