AIM: To evaluate the therapeutic effect and the indication of percutaneous ethanol injection (PEI),radiofrequency ablation (RFA) and their combination in treatment of hepatocellular carcinoma (HCC).METHODS: Two hundred and fifty-five patients with HCC received treatment of PEI, RFA or their combination.Group1 (＜ 3 cm in diameter, n=85) was treated with PEI,group2 (＜ 3 cm in diameter, n=153) with RFA. Group3(＞3 cm in diameter, n=86) was divided into two groups.Group 3a (n=34) was treated with RFA, while group 3b(n=52) was treated with RFA for 2 wk after transcatheter arterial chemoembolization or PEI. Contrast-enhanced sonography was performed for 61 patients before and after RFA. Liver function and serum alpha-fetoprotein (AFP) were measured for all patients. Changes of the lesions on ultrasound and contrast-enhanced CT/MRI were evaluated for assessing the therapeutic responses.The 1-, 2-, 3- and 5-year survival rates were recorded after treatment.RESULTS: In group 1, the complete necrosis rate of lesions after 1 mo was 77.6% (66/85). The level of AFP declined conspicuously after 1 mo. The 1-, 2-, 3- and 5-year survival rate after treatment was 80.0% (52/65),60.4% (32/53), 52.5% (21/40) and 33.3% (7/21),respectively. In group 2, the complete necrosis rate of lesions after 1 moh was 92.2% (141/153). The level of AFP decreased conspicuously after 1 mo. The 1-, 2-,3- and 5-year survival rate after treatment was 94.6%(88/93), 73.2% (52/71), 63.5% (33/52) and 46.4%(13/28), respectively. In group 3a, the complete necrosis rate of lesions after 1 mo was 23.5% (8/34). AFP dropped down to the normal level in only one patient after 1 mo. The 1-, 2- and 3-year survival rate after treatment was 47.6% (10/21), 42.9% (6/14) and 27.3%(3/11), respectively. Only one patient was still alive after 5 years. In group 3b, the complete necrosis rate of lesions after 1 mo was 57.7% (30/52). The level of AFP decreased after 1 mo. The 1-, 2-, 3- and 5-year survival rate after treatment was 68.6% (24/35), 46.2% (12/26),36.8% (7/19) and 27.3% (3/11), respectively.CONCLUSION: The therapeutic effect of RFA on small HCC is better than that of PEI. Small HCC is the optimal indication of RFA. For recurrent HCC (diameter＞3 cm),the combined treatment of RFA and PEI/ACE should be used.