To explore the relationship between serum cytokines and depression in epilepsy. Methods: A total of 766 patients diagnosed with epilepsy were selected for the study. Patients were evaluated by questionnaire and assessed using the Beck Depression Inventory-II (BDI-II) scale and epilepsy-related stigma score, and serum cytokine levels were measured. The data obtained were analyzed for statistical significance. Results: The prevalence of depressive disorder among patients with epilepsy was 30.3% . Of these, 41.3% , 34.4%, and 24.3% of patients were found to have mild, moderate, and severe depression, respectively. Logistic regression analysis showed that after correcting for confounding factors, compared with the first group of interleukin-6 (IL-6), the second, third, and fourth groups were risk factors for depression combined with epilepsy. On the other hand, compared with the first group of interleukin-10 (IL-10), second, third, and fourth groups were protective factors for depression combined with epilepsy. Conclusion: High level of IL-6 may be a risk factor for the incidence of depression in epilepsy. High level of IL-10 may be a protective factor for the incidence of depression in epilepsy