Helicobacter pylori (H. pylori) is a common organism in developing countries, it causes gastric disorders and cancer. Pathogenesis of these disorders involve cytokine gene polymorphisms that affect cytokine levels and clinical diseases. The aim of the study is to identify the relationship of IL-1β-511, IL-10-519 and TNF-α-308 polymorphisms to the risk of H. pylori infection and occurrence of gastric disorders. Subjects and methods: IL-1β-511, IL-10-519 and TNF-α-308 polymorphisms were assessed using polymerase chain reaction (PCR) restriction fragment length polymorphism technique (RFLP) in 356 subjects classified according to H. pylori infection and gastric disorders. Results: Carriers of T allele of IL-1β-511 and IL-10-519 had increased risk of H. pylori infection (OR:1.95, 95% CI:1.4-2.7, P<0.001 & OR:1.8, 95% CI:1.4-2.5, P<0.001; respectively). The IL-1β-511 and IL-10-519 T allele was associated with gastritis, peptic ulcer (PU) & gastric cancer (GC) (P< 0.001). Simultaneous occurrence of either IL-1β-511 TT or IL-10-519 TT genotypes with H. pylori significantly augmented the risk for different gastric diseases (gastritis; P=0.005 & 0.002, PU; P=0.01&0.02 and GC; P=0.02&0.01; respectively). While, the copresence of TNF-α-308 GA+ AA genotypes and H. pylori was related to gastritis only. Conclusion: This study revealed a significant association of the IL-1β -511C/T and IL-10-819C/T but not TNF-α-308 G/A polymorphisms with risk of Helicobacter pylori infection and different gastric diseases in Egyptian patients.