INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is projected to become the third leading cause of death worldwide. Despite extensive research over the past few decades, effective treatments remain elusive, making disease prevention and control a global challenge. METHODS: This study aimed to identify diagnostic key genes for COPD. We utilized the Gene Expression Omnibus database to obtain gene expression data specific to COPD. Differentially expressed genes (DEGs) were identified and analyzed through Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis. Integrated weighted gene co-expression network analysis was employed to examine related gene modules. To pinpoint key genes, we used SVM-RFE, RF, and LASSO. RESULTS: A total of 1782 DEGs were discovered, many of which were enriched in various biological pathways and activities. Four key genes- DISCUSSION: Our findings suggest that