Helicobacter pylori (Hp) is crucial in gastric carcinogenesis, but infection alone is not a sufficient cause, and the interaction between Hp infection and other risk factors has not been adequately studied. We conducted a pooled analysis of seven case-control studies from the Stomach cancer Pooling (StoP) Project, comprising 1377 cases and 2470 controls, to explore the interaction among Hp infection and tobacco smoking, alcohol drinking, socioeconomic status (SES) and dietary salt intake on the risk of gastric cancer. We estimated summary odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) by multivariate unconditional logistic regression. The analysis showed no consistent interaction between Hp infection and cigarette smoking, while interaction was more than multiplicative for alcohol drinking (OR = 1.38, 95% CI: 1.07-1.77, P-interaction 0.02) and high intake of salt (OR = 2.62, 95% CI: 1.88-3.65, P-interaction = 0.04). The interaction with SES followed the multiplicative model (P = 0.49), resulting in a weakening among infected individuals of the protective effect of high SES among observed Hp-negative individuals. The interactions found were more pronounced in subjects with history of peptic ulcer. The interactions with Hp infection were stronger for cigarette smoking and dietary salt in the case of noncardia cancer, and for alcohol and SES in the case of cardia cancer. No differences were found when stratifying for histologic type. This large-scale study aimed to quantify the interaction between Hp infection and other modifiable risk factors of gastric cancer revealed that the benefit of combined Hp eradication and lifestyle modification on gastric cancer prevention may be larger than commonly appreciated.