Objectives To explore the effect of oxcarbazepine combined with lamotrigine on the treatment of epileptic children and the levels of NSE and GFAP. Methods A total of 94 children with epilepsy treated in our hospital from January 2015 to December 2017 were randomly divided into the observation group and the control group. The control group was given oral oxcarbazepine, and the observation group was given lamotrigine on the basis of the control group for 6 months. The clinical efficacy, the incidence of adverse reactions and the changes of electroencephalogram before and after treatment were compared between the two groups, and the levels of NSE and GFAP were detected. Results After the treatment, the total effective rate of the observation group was 91.49%, the control group was 74.47% (χ2=10.260, P =0.001). The incidence of adverse reaction in the observation group was 8.51%, and the control group was 21.28% (χ2=6.431, P =0.011). After treatment, the θ frequency range in the observation group was lower than that in the control group (t =3.759, P =0.000), and there were no different for other frequency range. Conclusions The combination of oxcarbazepine and lamotrigine can effectively improve the therapeutic effect of epilepsy, reduce the incidence of adverse reactions during the medication and it was worthy of clinical application.