Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that causes obstructed airflow from the lungs. DNA methylation can regulate gene expression. Understanding the potential molecular mechanism of COPD is of great importance. The aim of this study was to find differentially methylated/expressed genes in COPD. DNA methylation and gene expression profiles in COPD were downloaded from the dataset, followed by functional analysis of differentially-methylated/expressed genes. The potential diagnostic value of these differentially-methylated/expressed genes was determined by receiver operating characteristic (ROC) analysis. Expression validation of differentially-methylated/expressed genes was performed by in vitro experiment and extra online datasets. Totally, 81 hypermethylated-low expression genes and 121 hypomethylated-high expression genes were found in COPD. Among which, 9 core hypermethylated-low expression genes (CD247, CCR7, CD5, IKZF1, SLAMF1, IL2RB, CD3E, CD7 and IL7R) and 8 core hypomethylated-high expression genes (TREM1, AQP9, CD300LF, CLEC12A, NOD2, IRAK3, NLRP3 and LYZ) were identified in the protein-protein interaction (PPI) network. Moreover, these genes had a potential diagnostic utility for COPD. Some signaling pathways were identified in COPD, including T cell receptor signaling pathway, cytokine-cytokine receptor interaction, hematopoietic cell lineage, HTLV-I infection, endocytosis and Jak-STAT signaling pathway. In conclusion, differentially-methylated/expressed genes and involved signaling pathways are likely to be associated with the process of COPD.