We report a case of advanced hepatocellular carcinoma (HCC) successfully treated by hepatic arterial infusion of 5-fluorouracil (5-FU) combined with systemic administration of interferon (IFN)-α and trans-arterial infusion (TAI) therapy of cisplatin (CDDP). A case was a 60-year-old man who had right upper abdominal pain and back pain. The abdominal CT revealed an early enhanced lesion in the posterior segment of the liver with portal vein and inferior vena caval tumor thrombi and multiple intrahepatic metastases. Tumor markers were elevated, AFP 2,480 ng/mL, PIVKA-II 31,900 mAU/mL. The patient underwent 4 courses of IFN-α/5-FU combination therapy and 8 times of TAI therapy of CDDP. After these therapies, tumors in the liver disappeared and tumor markers returned to the normal range. The patient is alive more than 58 months after the initial treatment. This case suggests that some patients with advanced HCC with tumor thrombus can get a long-term survival when intrahepatic lesions are controlled by various therapies including IFN-α/5-FU combination therapy.