ObjectiveTo investigate key differentially expressed genes (DEGs) in peripheral blood of idiopathic epilepsy patients, as well as their biological functions, cellular localization, involved signaling pathways, through bioinformatics analysis. So to provide new insights for the pathogenesis and prevention of idiopathic epilepsy.MethodsFirstly, we screened and downloaded microarray data including 6 peripheral blood samples of drug-naive patients with idiopathic epilepsy, 8 peripheral blood samples of responders of idiopathic epilepsy treated with Valproate (VPA), and 10 peripheral blood samples of non-responders of idiopathic epilepsy treated with VPA from Gene Expression Omnibus (GEO) data series GSE143272, which Public in January 2020. Secondly, we identified DEGs via the limma package and others in R software. Then we had gotten 74 DEGs, and subsequently conducted gene ontology and pathway enrichment analysis, PPI network analysis and hub gene analysis, using multiple methods containing DAVID, STRING, and Cytohubba in Cytoscape.ResultsWe had identified significant hub DEGs, including TREML3P, KCNJ15, ORM1, RNA28S5, ELANE, RETN, ARG1, LCN2, SLPI, HP, PGLYRP1, BPI, DEFA4, TCN1, MPO, MMP9, CTSG, CXCL8, RNASE3, RNASE2, S100A12, DEFA1B, DEFA1, DEFA3, CEACAM8, MS4A3, PTGS2, PI3, CCL3. The biological processes involved in these DEGs include immune response, inflammatory response, chemotaxis, etc. While, the molecular function is focused on peroxidase activity, chemokine activity, etc. Moreover, KEGG pathway enrichment analysis shows that DEGs were mainly involved in cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, chemokine signaling pathway and so on.ConclusionThese important key DEGs may be involved in the onset and development of idiopathic epilepsy through a variety of signaling pathways and complex mechanisms.