Chronic obstructive pulmonary disease is a complex pulmonary disease that causes airflow obstruction in humans. To identify the core genes in COPD pathogenesis, seven diverse microarray datasets (GSE475, GSE1122, GSE1650, GSE3212, GSE8823, GSE37768, and GSE22148) were downloaded from the gene expression omnibus database. All the datasets were analyzed independently with the R/Bioconductor package to screen the differentially expressed genes (DEGs). The gene ontology and pathway enrichment analysis were performed for the acquired DEGs using DAVID (Database for Annotation, Visualization, and Integrated Discovery). Further protein-protein interaction network was constructed for the DEGs and their potential hub genes and sub-networks were identified using Cytoscape software. From the selected seven datasets, 188 overlapped DEGs were perceived eventually based on considering the repetitive genes between at-least one dataset. Gene Ontology analysis reveals that most of the DEGs were significantly enriched in immune response, inflammatory response, extracellular region, lipid binding, cytokine, and chemokine activity. Moreover, genes from the sub-network analysis were again submitted to the DAVID server to validate the results which uncover the Toll-like receptor signaling pathway was significantly enriched and all the genes present in this pathway were likewise detected as hub genes from Cytoscape software. CXCL9, CXCL10, CXCL11, CCL4, TLR7, and SPP1 hub genes in the toll-like receptor signaling pathway were explored in this study as potential biomarker genes associated with COPD pathogenesis. © 2020 Taylor & Francis Group, LLC.