Objective：To explore the potential causal relationship between Helicobacter pylori（HP）infection and esophageal cancer （EC）. Methods：The analysis incorporated genome-wide association study（GWAS）data with HP infection as the exposure and EC as the outcome. A variety of Mendelian randomization（MR）methods were utilized，including inverse - variance weighted analysis， weighted median，MR - Egger，Simple mode，and Weighted mode to investigate the association between HP and EC. Additionally， Bayesian-weighted MR was introduced and the results were corrected using the false discovery rate（FDR）to enhance precision. The study also involved outlier detection，heterogeneity testing，sensitivity analysis，and pleiotropy assessment，as well as removing single nucleotide polymorphisms（SNP）potentially affected by confounding factors. For results that were particularly contentious，a meta - analysis was performed to provide a broader perspective. Potential reverse causation was assessed using Steiger testing and reverse MR. Furthermore，linkage disequilibrium score regression（LDSC）was utilized to evaluate the genetic correlation between HP and EC. Results：The comprehensive analyses showed that both traditional two -sample MR and Bayesian -weighted MR after FDR correction indicated no statistically significant causal association between HP and EC（P ＞ 0.05）. No pleiotropy was evident（P ＞ 0.05），and the robustness of the results was confirmed by the leave-one-out test. However，genetic correlation analyses of anti-HP IgG serum positivity and HP GroEL antibody levels suggested a potential genetic link with esophageal adenocarcinoma（P ＜ 0.05）. Conclusion：Despite the use of advanced statistical methodologies，the current evidence is insufficient to support a definitive causal association between HP and EC. This finding underscores the need for larger-scale GWAS data and more detailed subtype-specific analyses to further explore the association between these two conditions. Future research should include a broader range of populations and geographical areas to enhance the generalizability and applicability of findings，while also investigating the specific impacts of different HP strains and possible biological mechanisms，providing a stronger scientific support for the prevention and treatment of EC.