【Abstract】 Objective To study the efficiency and safety of combination of valproate and lamotrigine in the treatment of epilepsy. Methods 150 patients with epilepsy from March, 2014 to March, 2016 were randomly divided into control group and observation group treated with sodium valproate and sodium valproate combined with lamotrigine, respectively. The EEG results, the frequency of seizures, the scores of SES, the levels of serum TNFα and IL2 and the adverse reaction were compared between the two groups,. Results The improvement of EEG and the proportion of abnorma l discharge in the observation group were significantly lower than those in the control group (P＜005). The frequency of seizures in the observation group was significantly lower than that of the control group. The SES selfesteem scores of the observation group were significantly higher than those of the control group (P＜005). The levels of TNFα and IL2 in the peripheral blood of the observation group were significantly lower than those in the control group (P＜005). The adverse reaction rate of the observation group was significantly lower than that of the control group (P＜005). Conclusion Valproic acid sodium combined with lamotrigine has a good and stable effect on the treatment of epilepsy, can reduce the levels of serum TNFα and IL2, efficiently, and has a smaller side effect.