Background. The aim of this study is to investigate whether regional infusion of tumor necrosis factoralpha (TNF-α) and interferon-gamma (IFN-γ) could improve the therapeutic results of hepatic artery ligation (HAL) on liver cancer in a rat model. Methods. Morris hepatoma 3924A was implanted intrahepatically in 50 ACI rats. Two weeks after tumor implantation, 40 rats underwent hepatic artery cannulation and ligation. The cannula was connected to an infusion port implanted subcutaneously. Animals were then divided into four groups of 10 each to receive seven daily intraarterial injections of IFN-γ 100,000 IU/rat/day (HAL+IFN group), TNF-α 30 μg/rat/day (HAL+TNF group), IFN+TNF (HAL+IFN+TNF group), or normal saline solution (HAL group). The remaining 10 rats received a laparotomy only and served as untreated controls. Tumor volume, viable tumor area, and histopathology were assessed after 3 weeks. Results. The tumor growth was significantly retarded in the HAL group compared with the controls (tumor volume 683±245 mm 3 vs 2424±596 mm 3, p<0.05 ANOVA). HAL+TNF (221±93 mm 3) and HAL+IFN+TNF groups (74±31 mm 3), but not the HAL+IFN group (493±164 mm 3), were much more effective than the HAL group in controlling tumor growth (p<0.05). HAL+IFN+TNF achieved the best tumor control resulting in a 60% tumor-free rate (p<0.05 vs all other groups). Conclusions. These data suggest that HAL combined with regional infusion of TNF-α and IFN-γ significantly reduces tumor growth in a rat liver model. This attractive concept of combined modality therapy may have utility in the clinical setting in instances of unresectable liver cancer.