In non-resectable liver malignancies, concurrent administration of degradable starch microspheres (DSM) and anticancer drugs via hepatic artery has been suggested as a method to increase the concentration of drugs in tumor tissue. DSM also has been known to increase the temperature of tissue when administered at the time of hyperthermia. In the light of these findings, we have studied the effect of hepatic arterial infusion of 5-FU and mitomycin C and 2450 MHz microwave local hyperthermia in combination with hepatic arterial flow arrest with DSM for the treatment of hepatoma in 10 patients and metastatic liver cancer in 20 patients. Of the 8 patients with hepatoma with increased AFP, all the patients showed a decrease of AFP following therapy with an average decrease ratio of 64%. Of the 17 patients with hepatic metastasis with increased CEA, 16 patients (94%) showed a decrease of CEA following the therapy (control group with infusion chemotherapy and hyperthermia without DSM: 66%) with average decrease ratio of 50% (control group: 27%). Of the 15 patients with increased CA 19-9, 13 patients (86%) showed a decrease of CA 19-9 (control group: 62%) with an average decrease ratio of 52% (control group: 21%). This pilot study suggests that the concurrent hepatic arterial infusion of 5-FU, mitomycin C and DSM with local hyperthermia may have the potential to improve selective regional drug effect.