Objective To explore the mechanisms of epidermal homeostasis during aging. Methods Bioinformatic analysis software was used for GO analysis and KEGG signal pathway analysis based on microarray data [genes and microRNAs (miRNAs)]. Cytoscape (v. 3. 5. 1) was used to predict the miRNA?gene interaction network and key genes. Results The result of this study revealed the differential expression of miRNAs related to the human epidermis and that their target genes are involved in associated signaling pathways. Conclusions The identified epidermal signaling pathways provide a theoretical basis for improving the treatment of age?related skin diseases.