We report a case of advanced hepatocellular carcinoma (HCC) with tumor thrombosis extending from the inferior vena cava (IVC) towards the right atrium (RA) treated by radiation therapy (RT) and targeted therapy with sorafenib. A 55-year old man who had been a hepatitis C carrier eventually developed liver cirrhosis and primary HCC. Tumor thrombosis spanning across the IVC and the RA was noted at initial diagnosis. He received RT with 37.5 Gy in 15 fractions in addition to concurrent and sequential sorafenib therapy. Follow-up imaging studies showed complete response of IVC and RA thrombus.