Background: Gastric cancer is one the most diagnosed cancer and the third leading cause of death from cancer worldwide. As an indicator of antioxidant capacity thiol/disulfide homeostasis regulates detoxi- fication, cell signal mechanisms, apoptosis, transcription and antioxidant defense mechanisms. Disregulation of thiol/disulfide homeostasis identified in other cancer types by recent data. In this study, we aimed to evaluate the thiol/disulfide homeostasis in advanced gastric cancer patients. Methods: The patients who diagnosed with gastric cancer and healthy control subjects were included to study. Serum samples for the thiol-disulphide test were obtained at the time of diagnosis. Thioldisulphide homeostasis tests were measured by the automated spectrophotometric method. Thioldisulphide homeostasis was also measured according to clinical and laboratory features. Results: Thirty newly diagnosed advanced gastric adenocarcinoma patients and 28 healthy controls were enrolled in the study. The native thiol (NT) and total thiol (TT) levels of patients' group were significantly lower compared with controls (p ¼ 0.001 and p < 0.001). In the CEA high (5.4 ng/ml) group, DS/NT ratio were higher compared with CEA low (< 0.05 both). The correlation between CEA and DS levels was also significant (p ¼ 0.02). There was also a positive correlation between CEA levels and DS/NT ratio (p ¼ 0.01). Conclusion: Derangements of thiol/disulfide homeostasis may have a role in gastric cancer pathogenesis and the higher level of oxidative stress may relate to extensive and aggressiveness of the advanced disease. The diagnostic and prognostic values of thiol/disulfide products need to identify with further studies.