OBJECTIVES: Lung cancer is one of the most common causes of mortality all around the world. The increased production of reactive oxygen species occurs with cell damage, and cysteine is an important factor in preventing oxidative damage by its functional thiol group. The objective of this study was to evaluate the relationship between thiol/disulfide homeostasis (TDH) and the risk factors, disease severity, and physical condition of patients with lung cancer. MATERIALS AND METHODS: This is a prospective, controlled, nonblinded study, which included healthy volunteers and patients diagnosed with lung cancer who had not yet started any treatment. RESULTS: There were 45 male (90%) and five female (5%) patients (mean age 64±9 years), and 41 male (82%) and nine female (18%) healthy volunteers (mean age 65±17 years) were included in this research. Overall, the thiol levels were lower in patients than the control group (p<0.001). The native thiol level means were 275±72 μmol/l in the patient group and 414±80 μmol/l in the control group, and the total thiol level means were 309±74 and 451±79 μmol/l, respectively. However, the disulfide parameter was not statistically significantly different between the two groups. There were no correlations between the tumor size and overall survival and the total thiol, native thiol, and disulfide levels. CONCLUSION: This study showed that there is a significant relationship between lung cancer and TDH, but there were no correlations with the disease stage and the clinical performance status.