Abstract：Objective：To observe the clinical effect of Xingnaojing injection combined with citicoline sodium capsules for severe brain injury and its effect on contents of C-type natriuretic peptide(CNP) and insulin-like growth factor Ⅱ(LGF-Ⅱ) in serum. Methods：A total of 92 cases of patients with severe brain injury were selected and randomly divided into the control group and the study group，with 46 cases in each group. Both groups were given routine treatment；the control group was additionally treated with citicoline sodium capsules，and the study group was additionally treated with Xingnaojing injection based on the treatment of the control group. The clinical effects and the contents of LGF- Ⅱ and CNP in serum in the two groups were compared. Before and after treatment， the scores of National Institutes of Health Stroke Scale(NIHSS) and Toronto Clinical Scoring System(CSS)，and Barthel index in the two groups were evaluated. Results：The total effective rate was 95.7% in the study group and 78.3% in the control group，the difference being significant(P＜0.05). Before treatment， there was no significant difference being found in the comparison of levels of LGF- Ⅱ and CNP in serum between the two groups(P＞0.05)；after treatment，the levels of LGF-Ⅱ and CNP in serum in the study group were higher than those in the control group，the difference being significant(P＜0.05). Before treatment，there was no significant difference being found in the comparison of scores of NIHSS and CSS and the Barthel index(P＞0.05)；after treatment，the scores of NIHSS and CSS in the study group were lower than those in the control group(P＜0.05)， and the Barthel index was higher(P＜0.05). Conclusion： Xingnaojing injection combined with citicoline sodium capsules for severe brain injury can improve the clinical effect，the levels of CNP and LGF-Ⅱ in serum and the neurological function.