Radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) therapy are currently used for the treatment of hepatocellular carcinoma (HCC). The purpose of the study was to evaluate the usefulness of combination therapy of PEI and RFA (PEI-RFA). Twenty-three cirrhotic patients with 36 hepatic focal lesions which proved to be malignant by Fine Needle Aspiration Cytology (FNAC) or Fine Needle Aspiration Biopsy (FNAB) or Spiral C.T. were enrolled in the study. They were divided into two groups: group I, 12 patients (11 males and 1 female) with 21 HCCs (only 12 of them were treated) using RFA alone. Group II, 11 patients (9 males and 2 females) with 15 HCCs (only 12 of them were treated) using RFA after PEI. The other focal lesions in both groups were included and managed in other studies. The volume of coagulated necrosis and tumor ablation was estimated and compared in both groups. It was found that the number of ablated tumors in group II was significantly higher than that in group I (100% Vs 58.33%) with fewer treatment sessions required for complete tumor ablation. No major complications occurred in both groups. Results indicated that PEI-RFA is more effective than RFA alone and can make dramatic improvement of therapeutic effects in RFA therapy for HCC with fewer sessions of treatment.