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Objective Currently, existing studies lack specific long-term follow-up subgroup analyses for the Chinese population and fail to clarify how sample size and recruitment strategies affect the heterogeneous efficacy of Hp eradication. We therefore integrated data from Hp eradication therapy studies in Chinese Hp-positive patients with ≥3 years of follow-up, quantitatively analyzed the therapy’s impact on gastric cancer risk, and explored preventive effect differences across subgroups with varying sample sizes. This study aims to provide evidence-based support for clinical decision-making in gastric cancer primary prevention and the formulation of public health strategies. Methods We searched six major databases: PubMed, Embase, the Cochrane Library, Web of Science, Wanfang Database, and CNKI (China National Knowledge Infrastructure). The search included all relevant randomized controlled trials (RCTs) from each database’s inception to December 31, 2025. After screening based on inclusion and exclusion criteria, we used RevMan 5.3 software for risk of bias assessment, effect size pooling, and subgroup analysis. We assessed evidence quality using the GRADE approach. Results A total of 8 high-quality randomized controlled trials (RCTs) were included, with 260,609 participants (118,425 receiving Helicobacter pylori [Hp] eradication therapy). Pooled analysis showed that Hp eradication therapy significantly reduced gastric cancer risk by 18% (RR = 0.82, 95%CI: 0.73–0.91, P = 0.0004). Sample size subgroup analysis revealed that the conventional sample mixed group had a 45% lower gastric cancer risk (RR = 0.55), significantly outperforming the ultra-large sample community group (RR = 0.88). For follow-up duration, the subgroup with ≥10 years of follow-up showed a 47% reduction in gastric cancer risk (RR = 0.53, P<0.0001), while short-term intervention (≤5 years) showed a trend toward reduced risk without reaching statistical significance. Conclusion Helicobacter pylori (Hp) eradication therapy significantly reduces gastric cancer risk in Chinese Hp-positive individuals. It yields more pronounced benefits when participants are recruited via small- and medium-sized community screening or clinical channels, with clear gains observed in long-term follow-up (≥10 years). We recommend promoting this therapy among clinical high-risk populations and in precise community screening to enhance intervention cost-effectiveness. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261277174 , identifier CRD420261277174