Background and study aim: New therapeutic choices have been developed for hepatocellular carcinoma (HCC), including percutaneous ablation therapy, transarterial chemoembolization, radiation therapy and molecular target therapy. Ablation of liver tumors is currently the main alternative to formal liver resection. This work aimed at comparing percutaneous ethanol injection (PEI) with combined percutaneous ethanol and mitoxantrone injection (PIM) in treatment of HCC. Patients and methods: : This study included 125 patients with 131 HCC lesions which were randomly divided into two groups; group I composed of 68 lesions in 65 patients treated with PEI. Group II composed of 63 lesions in 60 patients treated with PEI and PIM. Clinical assessment, laboratory evaluation and CT studies were performed to all patients pre treatment and at 3, 6, and 12 months post treatment. Each focal lesion was considered as one subject. Results : : The percentage of ablation in both groups at 3, 6, 12 months were 60.3%, 48.5% and 39.7% in group I respectively versus 85.5%, 74.6% and 68% in group II respectively with a statistical significant difference between the two groups. There is an increased number of local recurrence in group I compared to group II. Side effects and complications are comparable in both groups. Conclusion : : Combination of PEI and PIM is better than PEI alone without additional complication and recurrence rate seemed to be better in combination therapy than PEI alone.