Introduction: Although there is accumulating evidence that genetic factors play a vital role in the pathogenesis of epilepsy, few epilepsy-associated genes have been identified. Additionally, the role of KCNJ15 in epilepsy has not been evaluated so far. Methods: Here, we performed differentially expressed gene analysis, expression quantitative trait loci analysis, gene co-expression analysis, and protein-protein interaction analysis to evaluate the role of KCNJ15 in epilepsy. Results: Analysis of gene expression and expression quantitative trait loci data revealed that KCNJ15 was significantly downregulated in patients with epilepsy (adjusted P = 0.0146 and log 2 Fold change = -1.0025), and an epilepsyassociated polymorphism (rs2833098) was linked to altered KCNJ15 expression level in human temporal lobe brain tissue (P = 0.0036). Gene co-expression analysis revealed that KCNJ15 was co-expressed with genes that have been reported to be associated with epilepsy in human brain tissue. Furthermore, protein-protein interaction analysis revealed strong supportive evidence for the role of KCNJ15 in epilepsy. Conclusion:Our results show that KCNJ15 may be a candidate target for epilepsy. Functional analysis of KCNJ15 may provide novel insights for epilepsy treatment.