The prognosis of hepatocellular carcinoma(HCC)with main portal vein(MPV)and/or the inferior vena cava(IVC)tumor thrombi is dismal. The management of HCC with severe tumor thrombus is complicated. In this study, we report a case of HCC with tumor thrombi in the MPV and IVC that was successfullytreated via liver resection and perioperative hepatic arterial infusion chemotherapy(HAI). A 68-year-old man was referred to our institution to treat huge HCC lesion in the right lobe of the liver. Abdominal computed tomography(CT)revealed a tumor(12 cm in diameter)in the right hepatic lobe and tumor thrombi in the MPV and IVC. The patient was initiallytreated with HAI(cisplatin 100mg/body). After 3 courses of HAI, the tumor was dramaticallyreduced in size, and the thrombus in the IVC had disappeared; however, the thrombus in the MPV remained. Therefore, we performed right hepatectomy, wedge resection of the IVC, combined resection of the MPV, and portal vein reconstruction. The histopathological findings of the resected specimen revealed that viable cancer cells were observed onlyin an 8×8mm lesion. Subsequently, HAI was performed as adjuvant therapy for 3 courses. The patient died of other causes 2 years 3 months after surgery. There was no sign of recurrence at the time of death. This case suggested that perioperative HAI and liver resection mayrepresent an effective treatment strategyfor HCC with severe tumor thrombus.