Background & Aim: Helicobacter pylori infection is a common problem in pediatric practice. Although the organism is thought to be responsible for many diseases, only a handful of them have a direct causal relationship.This work aimed to investigate the association between interleukin-8 (IL-8) -251 T/A and +781 C/T polymorphism and Helicobacter pylori (H. pylori) infection in children.Methods: This cross section study was conducted on 60 children with gastritis caused by H. pylori-infection and 60 gastritis children patients without H. pylori infection as a control group. All included patients were subjected to full history taking, complete clinical examination, abdominal ultrasound, laboratory assessment and upper GIT endoscopy, histopathology of gastric and duodenal biopsies and assessment of IL-8 -251 A/T and +781 C/T polymorphism. Results: IL-8 (-251 and +781) genotype polymorphism, were significantly associated with H.pylori infection. Patients with IL-8 (-251) A/T mutant type and patients with IL-8 (+781) C/T mutant type had statistically higher grades of chronic inflammation in stomach and higher frequencies of positive polymorph nuclear cell activity. Multivariate regression model showed that positive H. pylori stool antigen, mutant IL-8-251A/T and mutant IL-8+781C/T, were significant predictors of gastritis in the study participants. Conclusion: Heterozygous gene polymorphisms (-251 A/T and +781 C/T) was associated with the risk of developing gastritis in children with H. pylori infection. IL-8-251A/T and +781 C/T were significantly associated with severe gastritis in comparison with patient without H.pylori & gastritis.