OBJECTIVE： To observe therapeutic efficacy and safety of S-1 capsules combined with recombinant human endostatin in the treatment of middle and advanced primary liver carcinoma. METHODS： Totally 94 patients with middle and advanced primary liver carcinoma in the First College of Clinical Medical Science of China Three Gorges university during Feb. 2012-Dec. 2014 were divided into combination group （48 cases） and control group （46 cases） according to random number table. Both groups were given S-1 capsules 40-60 mg orally within 30 min after breakfast and supper. Combination group additionally received Recombinant human endostatin injection 150 mg added into 0.9％ Sodium chloride injection 210 mL with portable micro pump for continuous pump of 120 h. A course involved 14 d treatment and 7 d interval. Short-term objective therapeutic efficacy， clinical benefit response （CBR） and ADR were evaluated after 2 courses. Disease progression time and average survival period were compared between 2 groups. RESULTS： Objective response rate， disease control rate， disease progression time and average survival period of combination group were 14.6％， 66.7％， （5.5±1.3） months， （10.7±3.8） months； those of control group were 8.7％， 45.6％， （4.8±1.2） months， （8.9±3.3） months， with statistical significance between 2 groups （P＜0.05）. CBR rate of combination group（79.2％） was significantly higher than control group（52.2％）， with statistical significance （P＜0.05）. There was no statistical significance in the incidence of ADR between 2 groups （P＞0.05）. CONCLUSIONS： S-1 combined with recombinant human endostatin show good therapeutic efficacy and tolerance for patients with middle and advanced primary liver carcinoma， and do not increase the incidence of ADR.