Background: Helicobacter pylori is detected by pathogen recognition receptors including toll-like receptors (TLR) and nucleotide-binding oligomerization domain (NOD)-like receptors, eliciting an innate immune response against this bacteria. The aim of this study was to assess if polymorphisms of TLR2, TLR4, TLR5, NOD1 and NOD2 genes are associ‑ ated with gastric cancer, in particular in individuals infected with H. pylori. Results: A case-control study of 297 gastric cancer patients and 300 controls was performed to assess the associa‑ tion of 17 polymorphisms. Analyses performed under the allele model did not fnd association with gastric cancer. However, NOD1 rs2075820 (p.E266K) showed association with intestinal-type gastric cancer among H. pylori infected subjects (OR=2.69, 95% CI 1.41–5.13, p=0.0026). The association was not statistically signifcant in difuse-type gastric cancer cases (OR = 1.26, 95% CI 0.63–2.52, p=0.51). When the analyses were performed in patients carrying H. pylori strains harboring the cag pathogenicity island (cagPAI), we noticed signifcant association with NOD1 rs2075820 (OR=4.90, 95% CI 1.80–3.36, p=0.0019), in particular for intestinal-type gastric cancer cases (OR=7.16, 95% CI 2.40–21.33, p=4.1× 10−4 ) but not among difuse-type gastric cancer cases (OR=3.39, 95% CI 1.13–0.10, p=0.03). Conclusions: NOD1 rs2075820 increases the risk of intestinal-type gastric cancer among individuals infected with H. pylori, particularly in those harboring the cagPAI