Antitumor effects and prognosis of the patients with unresectable hepatocellular carcinoma were investigated in the treatment of chemo-embolization using degradable starch microspheres (DSM) and regional hyperthermia. Twenty-six cases were treated with chemo-embolization using DSM alone (Group A) and eighteen cases were treated with combination of chemo-embolization and hyperthermia (Group B). Tumor regression rates over 50% were 42% (11/26) and 56% (10/18) in Group A and Group B, respectively. In the patients with tumors over 7 cm in diameter, no favorable response was obtained in Group A (0/11), but the response rate was increased to 56% (5/9) by the combination of hyperthermia. In the patients with arterio-portal shunt, therapeutic effects were observed in 17% (1/6) and 50% (1/2) of Group A and Group B, respectively. In the patients with portal invasion (Vp2 and Vp3), no favorable response was demonstrated in Group A (0/4), but tumor response was demonstrated in one out of 3 cases in Group B. One- and two-year survival rates were 59% and 53%, respectively, in Group A, and 93% and 45%, respectively, in Group B. The DSM, temporary embolus, is suitable for the combination of hyperthermia because chemo-embolization using DSM can be performed many times. Therefore, these results suggested that chemo-embolization using DSM should be beneficial as combination therapy for unresectable hepatocellular carcinoma.