OBJECTIVE To compare the therapeutic effect and significance of different treatment methods for hepatocellular carcinoma (HCC) with portal vein tumor thrombi (PVTT). METHODS One hundred and forty-seven HCC patients with tumor thrombi in the main portal vein or the first branch of portal vein were divided into four groups. A, conservative treatment group (n = 18); B, hepatic artery ligation (HAL) and/or hepatic artery infusion (HAI) group (n = 18), periodically received postoperative chemoembolizations; C, excision of HCC with removal of PVTT group (n = 79); D, transcatheter hepatic arterial chemoembolization or portal vein infusion (PVI) or HAI after operation group (n = 32). RESULTS The median survival period was 2, 5, 12, and 16 months in group A, B, C, D, respectively. Their 1-, 3- and 5-year survival rates was 5.6%, 0 and 0 in group A; 22.2%, 5.6% and 0 in group B; 53.9%, 26.9% and 16.6% in group C; 82.8%, 48.8% and 41.3% in group D, respectively. The survival rates differed significantly between the 4 groups (P < 0.05). CONCLUSIONS Resection of cancer with removal of tumor thrombi for HCC with PVTT significantly improves the curative effect and quality of life. Local hepatic chemotherapy or chemoembolization after tumor resection with removal of tumor thrombi may further prolong survival period.