Objective:To evaluate the effect of the antioxidant tiopronin on chemotherapy in patients with advanced or metastatic non-small-cell lung cancer(NSCLC). Methods:Study subjects included the patients with advanced or metastatic NSCLC diagnosed and treated between June 2004 and December 2007 at Jiangsu Cancer Hospital & Research Institute. The patients(Group A)were treated with tiopronin combined with first-line chemotherapy. We ramdomly selected the same number of advanced or metastatic NSCLC patients who were not treated with tiopronin during first-line chemotherapy as control group(Group B). A total of 246 patients were enrolled. All data were analyzed using the State 8.0 statistical software. Results:The objective response rate of Group A versus Group B were 22.0% versus 19.5%(P=0.64),and disease control rate were 78.9% versus 74.0%(P=0.37),respectively. In Group B patients had higher neutropenia(54.4%)than that in Group A(41.5%)(P=0.041). The median progression-free survival of two groups were 6.2[95% confidence interval(CI),4.4~8.2]and 4.5(95%CI:4.2~6.4)months,respectively,with corresponding median overall survival were 11.8(95%CI:10.2~13.8)and 9.8(95%CI:8.7~11.3)months(P > 0.05). 1-year overall survival rates for patients in Group A and Group B were 48.8% and 35.8%(P=0.028),respectively. Conclusion:There were no differences in overall survival,progression-free survival,response rates and disease control rate between two groups,but tiopronin concurrent with first-line chemotherapy could reduce neutropenia and improve 1-year overall survival in patients with advanced or metastatic NSCLC.