A 73-year old man with multiple hepatocellular carcinomas underwent 4 transarterial chemoembolizations, but a tumor thrombus appeared in the left portal vein. The tumor sizes in segments 4 and 5 were 4.0 cm and 2.4 cm, respectively. The serum levels of AFP and PIVKA-II were 14,991 ng/ml and 15,944 mAU/ml, respectively. The tumor was 5-FU palpable in the epigastric region. Four ml of SMANCS and 4 ml of Lipiodol were injected to proper hepatic artery using the Seldinger technique. In addition, epirubicin (20 mg), MMC (4 mg) and Lipiodoi (2 ml) were injected into a proper hepatic artery via a reservoir every 3 weeks. The tumor was not palpable, and the tumor markers were markedly reduced after 2 months. The evaluation of response to the treatment was a partial response 3 months and 6 months later. Chemo-lipiodolization was very useful for advanced hepatocellular carcinoma with portal vein thrombus.