Background and Objective: Host genetic factors such as cytokine gene polymorphisms as well as Helicobacter pylori (H. pylori) infection have been found to be associated with gastric cancer risk . Interleukin 1 is a pro-inflammatory cytokine involved in H. pylori-induced gastric inflammation. Therefore, we analyzed the association between IL-1β and IL-1-RN polymorphisms and gastric cancer in Persian residents in north-eastern Iran. Methods: In a case-control study, the genotyping was carried out by PCR-RFLP in 109 gastric cancer patients and 101 randomly-selected healthy controls. The polymorphic sites include promoter region of IL-1β at 511 (C-T transition) position and IL-RN VNTR H. pylori infection was determined by ELISA assay in patients. Results: No significant differences were observed in the allele and genotype frequency of IL-1β-511 and IL-1RN VNTR between patients and control. Genotype frequencies in healthy controls were not significantly different from gastric cancer cases in separate histological types (intestinal or diffuse). IL- 1β-511 CT genotype frequency was significantly higher among healthy subjects than H. pylori positive gastric cancer patients (41.6% vs. 20%, p = 0.01, OR 0.30, 95% CI: 0.11-0.76). Meanwhile, relatively higher frequency of IL-1β-511 T genotype was observed among H. pylori positive cases as compared to healthy controls (42.9% vs. 26.7%, p = 0.06, OR 2.16, 95% CI: 0.96-4.8) Conclusion: Our results suggest the association between IL-1β-511 polymorphism and H. pylori infection and their contribution to the risk of gastric cancer. While IL-1β-511 CT genotype has a protective effect against H. pylori associated gastric carcinoma, IL-1β-511 TT may increase the risk.