The aim of this study was to compare the clinical outcome of percutaneous radiofrequency (RF) ablation, conventional percutaneous ethanol injection (PEI), and higher-dose PEI in treating hepatocellular carcinoma (HCC) 4 cm or less. A total of 157 patients with 186 HCCs 4 cm or less were randomly assigned to 3 groups (52 patients in the conventional PEI group, 53 in the higher-dose PEI group, and 52 in the RF group). Clinical outcomes in terms of complete tumor necrosis, overall survival, local tumor progression, additional new tumors, and cancer-free survival were compared across 3 groups. The rate of complete tumor necrosis was 88% in the conventional PEI group, 92% in the higher-dose PEI group, and 96% in the RF group. Significantly fewer sessions were required to achieve complete tumor necrosis in the RF group than in the other 2 groups (P < .01). The local tumor progression rate was lowest in the RF group (vs the conventional PEI group, P = .012; vs the higher-dose PEI group, P = .037). The overall survival rate was highest in the RF group (vs the conventional PEI group, P = .014; vs the higher-dose PEI group, P = .023). The cancer-free survival rate was highest in the RF group (vs the conventional PEI group, P = .019; vs the higher-dose PEI group, P = .024). Multivariate analysis determined that tumor size, tumor differentiation, and the method of treatment (RF vs both methods of PEI) were significant factors in relation to local tumor progression, overall survival, and cancer-free survival. The results show that RF ablation yielded better clinical outcomes than conventional and higher-dose PEI in treating HCC 4 cm or less.