Cigarette smoking is one of the risk factors in cardiovascular and respiratory diseases including atherosclerosis and chronic obstructive pulmonary disease (COPD). Although cigarette smoke mainstream consists of more than 4,500 chemical compounds, the compounds responsible for these diseases are still unknown. Cigarette smoke is divided in two phases: tar (particle) phase containing nicotine and gas phase. Airway epithelium cells are exposed both tar and gas phases. In this study, we have examined the effect of tar and gas phase of cigarette smoke on airway epithelium cells. The gas phase extract of cigarette smoke was prepared as previously described (Higashi et al., 2014, PLOS ONE 9: e107856). The tar phase extract of cigarette smoke was prepared by extracting tar phase on Cambridge filter with DMSO. Both tar and gas phases induced cell death in airway epithelial cells. The cell death induced by the gas phase was PKC-dependent, whereas the tar phase induced DNA double strand break and PKC-independent cell death. The pharmacological experiments revealed that the airway epithelium cell death by gas phase were ferroptosis. According to Yoshida et al., ferroptosis is involved in COPD pathogenesis (Yoshida et al., 2019, Nat Commun 10: 3145). Taken together, cigarette smoke gas phase might be a critical factor for cigarette smoking-induced COPD onset and development.