To investigate the possible association of polymorphisms, cyclooxygenase-2 (COX-2) promoter region -899G>C, COX-2 codon 587G>A, with risk of gastric cancer in the high incidence Hexi area of Gansu province in China. Blood samples from 140 patients with gastric carcinoma and 125 normal persons were collected in Hexi area of Gansu province in China. Polymorphisms of COX-2 -899G>A and COX-2 587G>A were genotyped by PCR-TaqMan. For detection Helicobacter pylori infection, Warhin-Starry staining was used. Three kinds of polymorphisms of COX-2 -899G>C were GG, GC and CC. The frequencies in gastric cancer patients were 72.9, 21.4 and 5.7%, and the frequencies in controls were 84.0, 12.8 and 3.2%, respectively. COX-2 -899C carrier (GC + CC) increased risk of gastric carcinoma with an odds ratio 1.950 (95% CI: 1.067-3.586, P=0.029). The genotype of COX-2 587G>A polymorphism were GG, GA and AA. The frequencies in patients group were 86.4, 11.4 and 2.2%, and the frequencies in controls were 89.6, 9.6 and 0.8%, respectively. There was no significant difference between cases and controls in each genotype. Helicobacter pylori infection rate was 68.6% in patients group and 50.4% in healthy controls. Helicobacter pylori infection rate in gastric cancer patients was remarkably higher than that in normal people (OR: 2.147, 95% CI: 1.302-3.541, P=0.003). Stratification analysis was showed that COX-2 -899C carrier genotype with Helicobacter pylori infection was significantly higher in cases than that in healthy controls (OR: 4.000, 95% CI: 1.638-9.770). The polymorphism of COX-2 -899G>C could be a risk factor for gastric cancer in high incidence Hexi area of Gansu Province in China. COX-2 -899C carrier genotype and Helicobacter pylori positive infection may have a synergistic effect on gastric cancer in high incidence Hexi area of Gansu Province in China. However, the polymorphisms of COX-2 587G>A is no association with gastric cancer in the high incidence Hexi area of Gansu Province in China.