Hepatic arterial infusion (HAI) chemotherapy has been selected as a therapeutic option for highly advanced hepatocellular carcinoma (HCC) with tumor thrombi in major portal branches or intrahepatic metastases. Conventional therapies have no clinical effect on highly advanced HCC. Recent advances of an implanted portcatheter system have facilitated repeated arterial infusion of chemotherapeutic agents, and HAI chemotherapy with several anticancer drugs provides a useful choice for advanced HCC. In various regimens of HAI chemotherapy, low-dose cisplatin and 5-fluorouracil (5-FU) therapy or combination therapy of interferon (IFN)-alpha/5-FU have been reported to improve the response rates for advanced HCC. However, the survival benefit of HAI chemotherapy may be affected by liver function. None of these regimens have been proved to be the standard for HAI chemotherapy. We previously reported that the beneficial effects of combination therapy of IFN-alpha/5-FU for advanced HCC. IFN-alpha/5-FU combination therapy may be a promising treatment modality for advanced HCC.