Abstract： Objective： To observe the clinical effect of Xingshen Huoxue Tongfu prescription combined with routine therapy for severe head injury. Methods：A total of 100 cases of patients with severe head injury were selected as the study subjects and divided into the control group and the observation group，with 50 cases in each group. The control group was given routine treatment，and the observation group was additionally treated with Xingshen Huoxue Tongfu prescription based on the treatment of the control group. The scores of Glasgow Coma Scale(GCS)，Glasgow Outcome Scale(GOS) and National Institutes of Health Stroke Scale(NIHSS)，and the levels of endothelin-1(ET-1) and C-reactive protein(CRP) before and after treatment， and the clinical effects and the improvement of sequelae after treatment in the two groups were compared. Results：The total clinical effective rate was 92.00% in the observation group，higher than that of 72.00% in the control group (P＜0.05). After treatment，the scores of GCS and GOS in the two groups were increased when compared with those before treatment(P＜0.05)，and the NIHSS scores and the levels of ET-1 and CRP were decreased(P＜0.05)；the scores of GCS and GOS in the observation group were higher than those in the control group(P＜0.05)，and the NIHSS score and the levels of ET- 1 and CRP were lower(P＜0.05). The total effective rate of improvement of sequelae was 94.00% in the observation group， higher than that of 78.00% in the control group(P＜0.05). Conclusion： Xingshen Huoxue Tongfu prescription combined with routine treatment can improve curative effect of severe head injury and prognosis，and reduce the incidence of sequelae.