We experienced a case of multiple hepatocellular carcinoma (HCC) complicated with N3 regional lymph node metastases. The gradual introduction of lymph node excision and high-dose chemotherapy using percutaneous isolated hepatic perfusion (PIHP) was effective in preventing progress of the tumor. The patient was a 63-year-old male who underwent a thorough medical examination because of elevated AFP at a local hospital. He was referred to our hospital. The preoperative laboratory results showed the elevation of AFP (729 ng/ml) and PIVKA-II (2,110 mAU/ml). CT scan of the liver revealed tumors in segment 4, 5 and 6, and lymph node metastases from the pancreas to the hepato-duodenal ligament. The enlarged lymph nodes were excised and the tumor in segment 5 was resected for pathological examination. Adriamycin was administered in doses of 100 mg/m2 and 80 mg/m2 using PIHP two and three months after the operation. According to the results of laboratory studies conducted 14 months after the operation, AFP was 12 ng/ml and PIVKA-II was within the normal range. CT scan of the liver showed the liquefaction degeneration of the remaining HCC. Although surgery is not generally indicated in a patient with multiple HCC complicated with N3 regional lymph node metastases, it should be considered in combination with PIHP in those with resectable extrahepatic lesion.