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Abstract Background We aimed to evaluate the clinical applicability of a new scoring system that comprises the variables age, sex, pepsinogen ratio (PGR), gastrin-17 (G-17), and Helicobacter pylori (Hp) infection for gastric cancer (GC) screening in the Wannan region, China. We also explored the risk factors of GC in the Wannan region. Methods We prospectively enrolled asymptomatic participants from January 1, 2019 to June 30, 2021 at the First Affiliated Hospital of Wannan Medical College. We used a receiver operating characteristic (ROC) curve to estimate the screening value of combined measurements of pepsinogen I, PGII, PGR, G-17, and Hp. Univariate analysis and multivariate analysis were used to explore the independent risk factors of GC. Results A total of 25,194 asymptomatic patients were eventually screened. The area under the ROC curve (AUC) of combined measurements was 0.817 (95% confidence interval [CI] 0.721–0.913), the sensitivity was 81.5%, and the specificity was 77.8%. The detection rate of this new scoring system for GC screening in low-, medium-, and high-risk groups was 0%, 1.63%, and 9%, respectively (P