AIM: To assess whether the effectiveness of a combination of transarterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) in the treatment of unresectable hepatocellular carcinoma (HCC) is superior to TACE alone a randomized controlled trial was performed.METHODS: The effect of combination therapy on longterm survival rates and duration of hospitalization was evaluated in 52 previously untreated HCCs, randomly allocated to TACE-PEI (27 pts) or TACE alone (25 pts).RESULTS: The cumulative survival rate of the TACE group was 75.8% at 6 mo, 62.9% at 12 mo, and 18.0% at 24 mo and of the TACE-PEI group 76.9%, 61.5%, and 38.7%,respectively. Comparison of overall survival in both groups showed no statistically significant difference. Regarding the patients with HCCs Okuda stage I (n = 26), the median survival of the TACE-PEI group was significantly longer(＞24 mo, median not yet reached in the study period)compared to the TACE group (18.4 mo [range 11.6-21.7 mo];P = 0.04). TACE-PEI reduced the relative risk for mortality to 0.4 (95%CI 0.15-0.96) compared to patients who received TACE alone. Median survival in patients with HCCs Okuda stage Ⅱ or Ⅲ was 5.0 mo in the TACE group (1.7mo-not defined) compared to 10.4 mo in the TACE-PEI group.CONCLUSION: The combination TACE-PEI improved survival time compared to TACE alone. Our study revealed a statistically significant improved survival in HCCs Okuda stage I. Side effects were minor and the combination therapy did not prolong duration of hospitalization considerably.