We report a case of hepatocellular carcinoma (HCC) treated successfully by transarterial chemoembolization (TACE) followed by combination therapy of 5-fiuorouracil (5-FU)and pegylated interferon-α (PEG-IFN-α). In the present case, the patient had massive and advanced HCC with a diameter of over 8 cm located in segment 7 (S7) of the liver.Furthermore, the tumor invaded into the major branch of the portal vein (Vp3). After TACE, combined administration of 5-FU and PEG-IFN-α was performed for 5 mo. HCC was totally eradicated and the serum levels of tumor markers were markedly decreased by the treatment. Although it has been reported that the combined use of conventional IFN-α and 5-FU showed striking effects on HCC in some cases, this case may suggest the more promising effect of PEG-IFN-α with a long-lasting effect, in the combined use with 5-FU for the treatment of massive advanced HCC.