The aim of this study was to characterize key biomarkers associated with pyroptosis in atopic dermatitis (AD). To identify the differentially expressed pyroptosis-related genes (DEPRGs), the gene expression profiles GSE16161 and GSE32924 from the Gene Expression Omnibus (GEO) database were utilized. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to determine the potential biological functions and involved pathways. Furthermore, protein-protein interaction network analyses were performed to identify hub genes. The types and proportions of infiltrating immune cells were detected by immune filtration analysis using CIBERSORT. A 12-axis competing endogenous RNA (ceRNA) network was constructed utilizing the miRNet database. Immunohistochemistry (IHC) further validated the differential expression of a key gene in the skin tissues collected from AD patients. The collection of skin tissue from human subjects in this study were reviewed and approved by the IRB of Yueyang Integrated Chinese and Western Medicine Hospital (KYSKSB2020-125). The study identified a total of 76 DEPRGs, which were enriched in genes associated with the inflammatory response and immune regulation. There was a higher percentage of activated dendritic cells and a lower percentage of resting mast cells in AD samples. expression was associated with upregulation of hub genes including and in the ceRNA network and was correlated with activated dendritic cells in AD. As a transcription factor, could regulate the production of downstream inflammatory factors. The IHC study revealed that was overexpressed in the skin tissues of AD patients, which were consistent with the results of the bioinformatic study. IRF1 and its related genes were identified as key pyroptosis-related biomarkers in AD, which is a crucial pathway in the pathogenesis of AD.