Cigarette smoke (CS) was known for its effect of increasing oxidative stress that could trigger tissue injury and endothelial dysfunction mediated by free radicals and reactive oxygen species (ROS). ROS itself is a key signaling molecule that plays a role in the development of inflammatory disorders. Nuclear factor erythroid2 related factor2 (Nrf2) is the main regulator of antioxidant cellular response to cell and tissue-destroying components caused by CS. Nrf2 protein that is significantly activated in the smokers' small airway epithelium is followed by a series of gene expression changes in the same cells. This study aims to observe differentially expressed genes (DEGs) in the human small airway epithelium of smokers compared to genes whose expression changes due to astaxanthin (AST) treatment, an antioxidant compound that can modulate Nrf2. Gene expression data that was stored in the GEO browser (GSE 11952) was analyzed using GEO2R to search for DEG among smokers and nonsmokers subject. DEG was further compared to those genes whose expression changes due to astaxanthin treatment (AST) that were obtained from the Comparative Toxicogenomics Database (CTD; https://ctdbase.org/). DEG (p<0.05) analysis result shows that there are 23 genes whose expression regulation is reversed compared to gene expression due to AST treatment. The gene function annotations of the 23 DEGs showed the involvement of some of these genes in chemical and oxidative stress, reactive oxygen species (ROS), and apoptotic signaling pathways. All of the genes were involved/associated with chronic bronchitis, adenocarcinoma of the lung, non-small-cell lung carcinoma, carcinoma, small cell lung carcinoma, type 2 diabetes mellitus, emphysema, ischemic stroke, lung diseases, and inflammation. Thus, AST treatment for smokers could potentially decrease the development of ROS and oxidative stress that leads to inflammation and health risks associated with smoking.