Diverse microbiotas which have some contributions to gene expression reside in human skin. To identify the protective role of the skin microbiome against UV exposure, proteinprotein interaction (PPI) network analysis is used to assessment gene expression alteration. A microarray dataset, GEO accession number GSE117359, was considered in this respect. Differential expressed genes (DEGs) in the germ-free (GF) and specific pathogen-free (SPF) groups are analyzed by GEO2R. The top significant DEGs were assigned for network analysis via Cytoscape 3.7.2 and its applications. A total of 28 genes were identified as significant DEGs and the centrality analysis of the network indicated that only one of the seven hub-bottlenecks was from queried genes. The gene ontology analysis of Il6, Cxcl2, Cxcl1, TNF, Il10, Cxcl10, and Mmp9 showed that the crucial genes were highly enriched in the immune system. The skin microbiome plays a significant role in the protection of skin against UV irradiation and the role of TNF and IL6 is prominent in this regard.