Objective: To investigate the efficacy and security of low molecular weight heparin (LMWH) as prophylaxis against venous thromboembolism (VTE) after primary hepatocellular carcinoma (PHC) surgery. Methods: One hundred and five patients who received PHC surgery were randomly designated to either anticoagulation therapy group (48 cases) or non-anticoagulation therapy group (57 cases). In the anticoagulation therapy group, the patients were subcutaneously injected with LMWH 5 000 U per day from 2nd day to 7th day after operations; however the patients in the non-anticoagulant therapy group were not received the anticoagulant therapy of LMWH after operation. The incidence of postoperative VTE, intra-abdominal hemorrhage, incision bleeding and skin ecchymosis around incision of the two groups were counted. Coagulation function in the 6th day and hemoglobin on the 1st and 6th day after operations were collected. The total abdominal drainage of the two groups was calculated after operation. Finally, a statistical comparison was made between two groups. Results: In the anticoagulant therapy group, there was no patients suffering from VTE (0/48). However, there were 5 patients suffering from VTE in the non-anticoagulant therapy group (5/57), which indicated the incidence of VTE was 8.87%. LMWH significantly decreased the incidence of VTE (P=0.043). Furthermore, there are no significantly statistical differences on the aspects of intra-abdominal hemorrhage, hemoglobin variation, abdominal drainage, coagulation function, incision bleeding and skin ecchymosis around incision between the two groups(P>0.05). Conclusion: Our study indicates that PHC surgery often leads VTE, which could be effectively and safely treated by LMWH.