Here, compared to normal gastric epithelial cell line and enzymatic dead mutant MnSOD H29A, we show that exogenous MnSOD treatment resulted in reduction of cell viability, colony formation, migration, and invasiveness; inhibition of SGC7901 xenograft growth; induction of apoptosis and arrest of G2-phase population in gastric cancer by an enzymatic activity-dependent manner; upregulation of p53, p21, and E-cadherin; and downregulation of cyclin D1 and N-cadherin. Here, SOD2 is linked to gastric cancer.