Objective To investigate the association between psychological stress and oxidative damage in TNM stage Ⅲ patients with poorly differentiated gastric adenocarcinoma (GA). Methods One hundred and six patients with newly diagnosed poorly differentiated GA were assessed using the Hamilton Depression Rating Scale (HAMD), Zung Self-rating Depression Scale (SDS), Zung Self-rating Anxiety Scale (SAS), Symptom Checklist 90 (SCL-90), activities of daily living (ADL) and other multiple-item questionnaires. Oxidative-stress-related parameters in serum and the expression of DNA repair genes were monitored during a pretreatment period. Results The patients were divided into depression and nondepression groups (Groups A and B, respectively) based on a HAMD score cutoff of 20. The mean SDS, SAS, SCL-90, ADL and passive coping scores were higher in Group A, whereas social support and quality of life were lower. Serum total antioxidant capacity, catalase, superoxide dismutase concentrations and anti-superoxide anion capacity (A-ASC) were significantly decreased in Group A, whereas serum malondialdehyde (MDA) and 8-hydroxy-deoxyguanosine (8-OHdG) levels were significantly increased. Pearson correlation analysis revealed that depression was positively correlated with MDA, SAS, SCL-90 and ADL, but negatively correlated with A-ASC. Furthermore, real-time PCR revealed that the expression levels of hOGG1 and APEX1 were increased in Group A. Conclusion Psychological stress might be related to impaired antioxidant system in patients with GA, and it presents the first evidence of the involvement of oxidative DNA damage in the pathogenesis of depression. Objective To investigate the association between psychological stress and oxidative damage in TNM stage III patients with poorly differentiated gastric adenocarcinoma (GA). Methods One hundred and six patients with newly diagnosed poorly differentiated GA were assessed using the Hamilton Depression Rating Scale (HAMD), Zung Self-rating Depression Scale (SDS), Zung Self-rating Anxiety Scale (SAS), Symptom Checklist 90 (SCL-90), activities of daily living (ADL) and other multiple-item questionnaires. Oxidative-stress- related parameters in serum and the expression of DNA repair genes were monitored during a pretreatment period. Results The patients were divided into depression and non-expression groups (Groups A and B, respectively) based on a HAMD score cutoff of 20. The mean SDS, SAS, SCL-90 , ADL and passive coping scores were higher in Group A, social support and quality of life were lower. Serum total antioxidant capacity, catalase, superoxide dismutase concentrations and anti- Pearson correlation analysis revealed that depression was positively correlated with MDA, SAS (8-OHdG) levels were significantly decreased in Group A, and serum levels of 8-hydroxy-deoxyguanosine However, real-time PCR revealed that the expression levels of hOGG1 and APEX1 were increased in Group A. Conclusion Psychological stress might be related to impaired antioxidant system in patients with GA , and it presents the first evidence of the involvement of oxidative DNA damage in the pathogenesis of depression.