Abstract: OBJECTIVE To explore the relationship between Helicobacter pylori infection with cytotoxin-associated gene-A(CagA) and gastric cancer and the effects on somatostatin, nuclear factor kappa B(NF-κB) and cyclooxygenase 2(COX2). METHODS A total of 128 patients with gastric mucosa lesions in our hospital were selected as study subjects, including 44 patients with chronic superficial gastritis, 38 patients with atrophic gastritis, and 46 patients with gastric cancer. Enzyme-linked immunosorbent method was used to determine the serum CagA-IgG and somatostatin levels. The gene expressions of NF-κB and COX2 were detected by immunohistochemical SP method. RESULTS The positive rate of CagA in gastric cancer group was 73.9%, which was significently higher than that in superficial group and shrinkage group (50.0% and 52.6%, P<0.05). Somatostatin level in gastric cancer group was obviously lower than that in superficial group and shrinkage group (P<0.05). Somatostatin level in the shrinkage group was significently lower than that in superficial group (P<0.05). Somatostatin level in CagA positive patients was significently lower than that in CagA negative patients (P<0.05). The positive rates of NF-κB and COX2 in gastric cancer group were significently higher than those in superficial group and shrinkage group (P<0.05), and in shrinkage group were significently higher than those in superficial group(P<0.05). The positive rates of NF-κB in CagA positive patients in gastric cancer group and shrinkage group were obviously higher than that in CagA negative patients (P<0.05). The positive rate of COX2 in CagA positive patients in gastric cancer group was significently higher than that in CagA negative patients (P<0.05). CONCLUSION There is close correlation between CagA positive Hp infection and gastric mucosal carcinogenesis, which is easier to reduce the somatostatin level and increase NF-κB and COX2 positive expressions.