AbstractBackground. Among the diseases of oral mucosa, oral lichen planus (OLP) is characterized by chronic autoimmune/autoinflammation. However, the etiology and pathogenesis of OLP were still limited. The aim of this research was to identify the differentially expressed genes and their potentially interacted miRNAs in OLP to provide a possible explanation of the pathogenesis of OLP and therapeutic biomarkers.Methods. The OLP microarray dataset (GSE52130) was download from the Gene Expression Omnibus (GEO) database. R software was used to identify differentially expressed genes between the OLP samples and normal oral mucosa. Functional enrichment analysis of DEGs, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, were conducted. Protein–protein interaction (PPI) network analysis was performed in the STRING database. CytoHubba in the Cytoscape software was applied to determining the top 10 hub genes, whose relative miRNA was identified through RNA Interactome Database.Results. Overall, 627 DEGs was identified in OLP samples, including 351 highly expressed genes and 276 lowly expressed genes. GO analysis indicated that the epidermal differentiation was mostly enriched. For the KEGG pathway, the DEGs in OLP samples were mostly involved in Staphylococcus aureus infection, Estrogen signaling pathway, Serotonergic synapse and Histidine metabolism. Top 10 hub genes including LOR, LCE3D, LCE3E, LCE1B, LCE2B, SPRR2E, SPRR2G, LCE2A, RPTN and CDSN were identified from the PPI network. The miRNA (hsa-miR-98-5p) was regarded as the mostly possible miRNA involved in OLP.