BACKGROUND/AIMS: The purpose of this study is to evaluate the effect of radiation therapy (RT) for tumor thrombosis (TT) in the major portal vein (PV) or inferior vena cava (IVC) from unresectable hepatocellular carcinoma. METHODOLOGY: Fifteen HCC patients with main PVTT (n = 10) and IVCTT (n 5) were treated with three-dimensional conformal RT between 2001 and 2004. The mean dose was 38.5 Gy (range 28 to 54Gy). The concurrent therapies to intrahepatic tumor included transcatheter arterial chemoembolization (TACE) in 7, TACE + hepatic arterial infusion in 2 and systemic chemotherapy in 1 patient. The therapeutic effect was assessed by tumor regression for TT. RESULTS: An objective response was observed in 3 of 15 patients (20%). There were no patients with progressive disease. The median survival time was 10 months. In 12 cases with stable disease, time to progression (TTP) estimated above 6 months were 42% (5/12 cases). In univariate analysis, therapeutic effect and TTP were affected to survival time. All patients did not have severe deterioration of liver function. CONCLUSIONS: In the current study, we concluded that RT was superior treatment in terms of local control capability and was useful to continue further treatment because RT did not make liver function worse.