Laser therapy is known as an efficient approach in dermatology surgery. CO2 laser therapy is a gold standard treatment in skin surgery. This study aimed to evaluate the interferons change after CO2 laser surgery Significant differentially-expressed genes (DEGs) of arm skin after 7 days of treatment by the CO2 laser relative to the controls are downloaded from Gene Expression Omnibus (GEO) and are included in the protein-protein interaction network via a STRING database (an application of Cytoscape software). The central DEGs were identified and enriched via gene ontology by using Clue GO software. A network including 78 DEGs and 100 neighbors was constructed and STAT1, MX1, ISG15, OAS1, IFIT1, IRF8, OASL, OAS2, and RSAD2 as hubs and STAT1, PTPRC, MX1, IRF8, ISG15, IL6, RORC, SAMSN1, and IFIT1 as bottlenecks were introduced. The cytokine-mediated signaling pathway, interferon gamma signaling, hepatitis C, interferon alpha/beta signaling, and the type I interferon signaling pathway were identified as 5 clusters of biological terms which are related to the central nodes. It can be concluded that the cytokine-mediated signaling pathway is the major pathway that is dysregulated after laser application in the treated skin.