Objective To analyze the differential genes of chronic bronchitis phenotype and emphysema phenotype in patients with chronic obstructive pulmonary disease（COPD）by bioinformatics method，and to explore the possible molecular pathogenesis of different clinical phenotypes of COPD. Methods The transcriptomic data GSE69818 of lung tissue of COPD patients with chronic bron⁃chitis phenotype and emphysema phenotype were downloaded from GEO database，and the differential genes were obtained by Rank Prod. Further function and pathway enrichment analysis of differentially expressed genes were carried out by DAVID database. The protein-protein interaction（PPI）networks were established using STRING to identify key genes. Results A total of 3 734 DEGs were obtained，of which 1 661 genes were up-regulated and 2 073 genes were down-regulated in emphysema group. Geneontology indicated that the DEGs were mainly involved in immune response，endoplasmic reticulum calcium homeostasis and extracellular structure，and KEGG pathway involved bacterial invasion of epithelial cells，extracellular matrix（ECM）-receptor interaction，CGMP-PKG signaling pathway and primary immunodeficiency. Ten hub genes were recognized by PPI analysis，including ACTB，ITGB1，RHOA，FN1，SRSF1， CAV1，CTNNA1，VEGFA ，HNRNPA1 and APP. There were 9 down-regulated genes （APP，ITGB1，FN1，RHOA ，CAV1，CTNNA1， VEGFA ，HNRNPA1，SRSF1）and 1 up-regulated gene（ACTB）. Conclusion The key genes and signal pathways involved in the devel⁃opment of chronic bronchiolitis and emphysema in COPD patients could be obtained through bioinformatics analysis，which provided po⁃tential targets for precise treatment of COPD.