Abstract: Objective To explore and analyze the preventive effect of sodium valproate on epileptic patients with severe traumatic brain injury after operation. Methods 60 cases of severe craniocerebral injury patients in our hospital from December 2014 to December 2015, were randomly divided into observation group and control group, 30 cases in each group. The observation group received preoperative valproate treatment, and patients in the control group were not given valproate. Before and after the operation of neurocognitive assessment of patients, observation and analysis of the test results. Results the rank sum test, two groups of patients with postoperative epilepsy (u=2.35, P < 0.05) difference obvious. Observation group only 1 case of cerebral attack and control group with cerebral attack primarily, and always occur rate was significantly higher than that of the control group (P < 0.05, X2=4.21), with statistical significance. The two groups of patients before and after the operation MOCA scores between groups and between groups. Multi time, multi time difference has statistical significance (F=11.535, P = 0.001, F=5.835, P = 0.02, F=4.921, P = 0.03), with the passage of time, the cognitive function of patients in two groups were significantly improved, but the postoperative 3M observation group MOCA score was significantly higher than that of control group (P < 0.05), with statistical significance. During follow-up, within 3 days after the operation to observe group 1 patients with diarrhea, nausea and vomiting occurred in 2 cases, 2 cases of headache, subsequent follow-up of 3 months and no severe thrombocytopenia and pancreatitis and acute liver necrosis, and with patients in the control group had no significant difference (P < 0.05), does not have statistical significance. Conclusion for the patients with severe craniocerebral injury, preoperative given sodium valproate can effectively prevent epilepsy, and reduce neurocognitive function in patients with decreased after surgery, is worthy of clinical application.