Background: Epilepsy is a complicated neurological disorder with almost 30% refractory. Recent years, several studies showed that epilepsy is associated with its comorbidities by shared molecular mechanisms. However, the association of epilepsy and digestive comorbidities are still unclear. In this study, we aim to explore the association between inflammatory bowel disease (IBD) and epilepsy, and to find promising therapeutic targets for refractory epilepsy. Methods: Two gene expression profiles (GSE134697 and GSE59071) were selected from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by GEO2R and the DESeq2 package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of intersection DEGs and Gene Set Enrichment Analysis (GSEA) were conducted by clusterProfiler package. The protein-protein interactions (PPI) network was established by using STRING and visualized by Cytoscape. Genes in the most significant module identified by MCODE plug-in were considered as candidate hub genes. Validation of hub genes were performed by using the GSE143272 dataset. Results: Cytokine-cytokine receptor interaction pathway is identified as a communal pathway between IBD and epilepsy. CXCL8, CXCR4 and ITGAX were identified as the hub genes. Conclusions: The identification of the communal pathway and hub genes in this study contributes to a potential novel therapeutic target in refractory epilepsy.