Oxidative stress is considered as risk factors for the development of POAG. SOD2 plays an important role in many biological processes caused by ROS. We performed a study to investigate the association of two common SNPs in SOD2 (rs2842980 and rs4880) with the risk of POAG, and the interaction between SOD2 polymorphisms and environmental factors. 170 patients with POAG and 340 matched healthy controls were collected into this study without blood relationship. Genotyping of SOD2 rs2842980 and rs4880 was conducted in a 384-well plate format on the sequenom MassARRAY platform. The association between SOD2 rs2842980 and rs4880 and risk of POAG was analyzed by logistic regression analyses. Compared with the TT individuals, individuals with the TC and CC genotypes have a substantial increased susceptibility for POAG incidence, and adjusted ORs (95% CI) were 1.63 (1.03-2.58) and 6.92 (2.12-22.62), respectively. Moreover, the C allele displayed a 2.09 folds risk of POAG in comparison to the T allele (adjusted OR: 2.09, 95% CI: 1.43-3.06). We found that the rs4880 showed interaction with age. In conclusion, our study suggests a significant association between rs4880 polymorphism and risk of POAG in the Chinese population. SOD2 rs4880 polymorphism could be a susceptibility biomarker for POAG.