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AIM: To investigate the relationship between the expression of pepsinogen C (PGC) and gastric cancer, precancerous diseases, and Helicobacter pylori ( H pylori) infection. METHODS: The expression of PGC was determined by immunohistochemistry method in 430 cases of gastric mucosa. H pylori infection was determined by HE staining, PCR and ELISA in 318 specimens.RESULTS: The positive rate of PGC expression in 54 cases of normal gastric mucosa was 100%. The positive rates of PGC expression in superficial gastritis or gastric ulcer or erosion, atrophic gastritis or gastric dysplasia and gastric cancer decreased significantly in sequence (P＜0.05;100%/89.2% vs 14.3%/15.2% vs 2.4%). The overexpression rate of PGC in group of superficial gastritis with H pylori infection was higher than that in group without H pylori infection (P＜0.05; χ2= 0.032 28/33 vs 15/25).The positive rate of PGC expression in group of atrophic gastritis with H pylori infection was lower than that in group without H pylori infection (P＜0.01; χ2 = 0.003 4/61vs 9/30), and in dysplasia and gastric cancer. CONCLUSION: The level of PGC expression has a close relationship with the degree of malignancy of gastric mucosa and development of gastric lesions. There is a relationship between H pylori infection and expression of antigen PGC in gastric mucosa, the positive rate of PGC expression increases in early stage of gastric lesions with H pylori infection such as gastric inflammation and decreases during the late stage such as precancerous diseases and gastric cancer. PGC-negative cases with H pylori-positive gastric lesions should be given special attention.