OBJECTIVES The association of interleukin-1B (IL-1B)-511 polymorphism with gastric cancer is still controversial, and the association of IL-1B-511 polymorphism with subtypes of gastric cancer is still largely unknown. We investigated whether the association between IL-1B-511 polymorphism and gastric cancer risk varies by clinically important tumor characteristics and the prognostic value of this polymorphism in a large population-based case-control study among Chinese. METHODS A population-based case-control study was conducted between 1999 and 2006 in Guangdong Province, China. A total of 1,010 gastric cancer patients and 1,500 healthy controls were enrolled in this study. Polymorphism in IL-1B-511 was analyzed by PCR-restriction fragment length polymorphism on 501 gastric cancers and 500 healthy controls. RESULTS Compared with the CC genotype, carriers of IL-1B-511 TT genotype had an increased gastric cancer risk (odds ratio (OR)=1.97, 95% confidence interval (CI)=1.29-3.01, P=0.0016). TT genotype was significantly associated with intestinal type of gastric cancer (OR=3.16, 95% CI=1.74-5.71, P=0.0001) but not with diffuse or mixed-type gastric cancer. The test for OR heterogeneity between the intestinal-type and non-intestinal-type gastric cancers was statistically significant (P=0.02). In subgroup analyses, TT genotype was found to be associated with poorly differentiated gastric cancer (OR=3.31, 95% CI=1.43-3.60, P<0.0001), but not with moderately or well-differentiated gastric cancer. IL-1B-511 genotypes were not associated with the prognosis of gastric cancer patients. CONCLUSIONS IL-1B polymorphism influences certain subtypes of gastric cancer according to the clinical and pathological features. Understanding the etiologic heterogeneity of gastric cancer may result in improvements in controlling this disorder.