Cigarette smoking is one of the risk factors for respiratory diseases such as chronic obstructive pulmonary disease and emphysema. Cigarette smoke can be divided into two phases; tar (particle) phase including nicotine and gas phase. Although both phases of cigarette smoke have cytotoxic activity and affect respiratory system, the molecular mechanism for cytotoxicity has remained to be clarified. In this study, we have examined the effects of cigarette smoke extracts on tracheal epithelial cells and lung cells. Both tar and gas phases induced cell death. Ferrostatin-1 suppressed gas phase-induced cell death, whereas it had no effects on tar phase-induced cell death. Several unsaturated carbonyl compounds such as acrolein (ACR) and methyl vinyl ketone (MVK) are major cytotoxic compounds in the gas phase. Ferrostatin-1 also suppressed ACR- and MVK-induced cell death in tracheal epithelial cells. These results indicate that ACR and MVK in gas phase are critical factors for ferroptosis induction by cigarette smoke in the respiratory system. Since we have previously reported that ACR- and MVK-induced cell death is PKC-dependent in aorta smooth muscle cells, we have examined PKC inhibitors. The results suggest that novel and/or atypical PKCs involve in cigarette smoke-induced ferroptosis induction in tracheal epithelial cells.