Objective To compare the effect of hyperfractionation radiotherapy combined with hepatic artery catheterization chemotherapy and hepatic artery ligation (group A, 65 patients) with conventional fractionation radiation combined with hepatic artery catheterization chemotherapy and hepatic artery ligation (group B, 65 patients) for unresectable primary liver cancer.Methods A total of 130 stage Ⅱprimary liver patients confirmed by pathology and evaluated as unresectable by exploratory laparotomy were divided evenly into group A and group B by the sequence of exploration. The two groups were comparable in age, sex, tumor type and positive fetal protein (AFP). Group A patients were treated by hepatic artery chemotherapy (PDD, 10 mg/day) 6 days a week with hepatic artery ligation followed by hyperfractionation radiotherapy (250 cGy/f, bid) 3 days a week with the scheme alternated weekly. Group B patients were treated by conventional fractionation radiotherapy with the same scheme of chemotherapy as group A. The total dose of PDD and radiotherapy for both groups were 240 mg and 45Gy. Results The AFP level was reduced to half in 89.7% of patients in group A and 67.6% in group B. The 1 , 3 and 5 year survival rates were 90.8%, 63.1%, 23.1% for group A and 73.9%, 41.5% 9.2% for group B, the difference was statistically significant (P0.05). Conclusions Hyperfractionation radiotherapy combined with hepatic artery catheterization chemotherapy and hepatic artery ligation is an effective and reasonable therapeutic scheme for unresectable liver cancer. It can effectively relieve symptoms, reduce the tumor, increase second surgical resection rate and prolong the survival. At the same time, the operation is simple and relatively easy.