Objective: To explore the application value of oxcarbazepine and levetiracetam in patients with focal epilepsy and its effect on serum miR-23a-3p and miR-146a levels. Methods: A total of 120 patients with focal epilepsy were divided into the combination group (treated with oxcarbazepine combined with levetiracetam, n=60) and the conventional group (treated with oxcarbazepine alone, n=60) according to the different treatment methods. Both groups of patients continued treatment until the end of the cycle. The efficacy, nerve injury markers, serum miR-23a-3p and miR-146a levels, abnormal discharges in the electroencephalogram, prognosis, and safety were compared between the two groups. Results: After treatment, the total effective rate in the combination group was higher than that in the conventional group (P<0.05). After treatment, both groups showed increases in brain-derived neurotrophic factor (BDNF) (P<0.05), and the combination group was higher than the conventional group (P<0.05). The levels of S100B and NSE were both reduced (P<0.05), and the combination group was lower than the conventional group (P<0.05). The QOLIE-31 score and MoCA score both increased (P<0.05), and the combination group was higher than the conventional group (P<0.05). Epileptiform discharges and the number of involved leads, serum miR-23a-3p and miR-146a levels in both groups decreased compared to those before treatment (P<0.05). Meanwhile, these parameters in the combination group were lower than those in the conventional group (P<0.05). Conclusion: Combined use of oxcarbazepine and levetiracetam in the treatment of focal epilepsy can improve clinical efficacy, and is superior to conventional treatment in improving abnormal discharges in the electroencephalogram and prognosis. The mechanism may be related to synergistic downregulation of serum miR-23a-3p and miR-146a levels and the promotion of neural restoration.