INTRODUCTION: Gene expression profiles of peripheral blood monocytes from patients with non-small cell lung cancer (NSCLC) before and after chemotherapy were used to investigate the effect of chemotherapy on gene expression. MATERIALS AND METHODS: Microarray dataset GSE39345 was downloaded from Gene Expression Omnibus, including 32 NSCLC samples before chemotherapy, 17 NSCLC samples after chemotherapy and 20 healthy samples. Raw data pretreatment and differentially expressed genes (DEGs) analysis between health and NSCLC samples before chemotherapy, health and NSCLC samples after chemotherapy were performed with packages of R. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was done for the common DEGs with WebGestalt to investigate their underlying function. RESULTS: A total of 904 DEGs were identified in health vs. NSCLC samples before chemotherapy and 2148 in health vs. NSCLC samples after chemotherapy. Further, they were divided into three sets: 584 common DEGs, 320 unique DEGs (health vs NSCLC samples before chemotherapy), and 1564 unique DEGs (health vs NSCLC samples after chemotherapy). Function enrichment analysis showed that these common DEGs were associated with cell cycle and cell differentiation. CONCLUSIONS: Chemotherapy could not completely reverse the lung cancer development because several cell growth-related genes are still present even after chemotherapy.