Gastric Cancer (GC) is the fifth leading cancer in the world and the third leading cause of cancer-related death. The 5-year survival rate of advanced gastric cancer is less than 30%, it is very important to prevent gastric cancer. Current methods to prevent gastric cancer are eradication of H. pylori, early endoscopic diagnosis and early treatment. Chemoprevention of cancer is using of natural, synthetic, or biological substances to prevent, or reverse the development of cancer, thereby reducing the incidence and mortality of cancer. We will discuss the target of chemoprevention for gastric cancer based on the clue of regeneration of gastric mucosal epithelium from the perspectives of gastric stem cell proliferation and differentiation.