The direct effect of intact Helicobacter pylori on gastric epithelial cells SGC-7901 and the protection given by the antioxidants vitamin C and sodium selenite were studied. Incubation of SGC-7901 cells with H. pylori simultaneously caused a significant increase of DNA damage (DNA strand breakage and DNA fragmentation) and ROS formation, as well as a significant decrease of intracellular GSH content in a H. pylori multiplicity of infection (MOI) dependent manner in gastric cells. ROS formation was strongly positively correlated while GSH content was negatively correlated with DNA strand breakage and fragmentation, indicating that DNA damage may be mainly caused by H. pylori-induced oxidative stress in gastric cells. The antioxidants, vitamin C and sodium selenite, directly increased GSH content while diminishing ROS formation and DNA damage in H. pylori-infected SGC-7901 cells, indicating that vitamin C and sodium selenite can protect gastric cells against H. pylori damage. The protections by vitamin C and sodium selenite further demonstrated that DNA damage may be derived from oxidative stress in H. pylori-infected gastric cells. The results suggested that DNA damage caused by H. pylori-induced oxidative stress may be one important factor in the pathogenesis of H. pylori, and that vitamin C and sodium selenite may have a preventive or therapeutic role against H. pylori-associated gastric diseases.