Objective To analyze the application value of serum gastrin 17 (G⁃17), pepsinogen (PG)Ⅰ, PGⅡ, and PGⅠ⁃to⁃PGⅡ ratio (PGR) in gastric cancer screening, and to explore the effect of gastric cancer screening based on Hangzhou population characteristics⁃constructed ABC method (Hangzhou ABC method). Methods (1) Establishment stage: a total of 1747 healthy check⁃up individuals (high⁃risk population for gastric cancer) were selected from two Hangzhou hospitals. All individuals underwent examination of serum G⁃17, PGⅠ and PGⅡ levels, and gastroscopy. The optimal cut⁃off values for various indices in diagnosing gastric cancer were determined using receiver operating characteristic curves, and the diagnostic performance when used them alone or in combination was evaluated. (2) Validation stage: a total of 22 133 healthy check⁃up individuals from Hangzhou multiple hospitals were selected, and their levels of serum G⁃17, PGⅠ and PGⅡ were detected. Risk stratification was performed on all research subjects using the new ABC method and the Hangzhou ABC method, and gastroscopy was recommended for medium⁃ and high⁃risk groups, while the low⁃risk group was followed up for 5 years. Gastric cancer detection rate and diagnostic performance were compared between the two methods. Results (1) Among 1747 healthy check⁃up individuals, 59 were diagnosed with gastric adenocarcinoma (the gastric cancer group) and 1608 had no gastric tumors (the non⁃gastric tumor group). Serum PGⅠ level and PGR in the gastric cancer group were lower than those in the non⁃gastric tumor group, while serum G⁃17 level was higher than that in the non⁃gastric tumor group (P<0.05). However, no statistically significant difference in PGⅡ level was observed between the two groups (P>0.05). (2) Establishment stage: G⁃17, PGⅠ, and PGR were enrolled in the analysis. The optimal cut⁃off values for the three in diagnosing gastric cancer were 9.78 pmol/L, 75.53 μg/L, and 4.98, respectively. When using a single indicator for gastric cancer diagnosis, only PGR achieved a sensitivity >80%, with a relatively larger area under the curve (AUC) of 0.706. When using combined indicators, the AUC for PGR combined with G⁃17, PGR combined with PGⅠ, and PGR combined with G⁃17 in diagnosing gastric cancer were 0.690, 0.625, and 0.634, with sensitivities of 94.9%, 71.2%, and 96.6%, respectively. Among these, the sensitivity of PGR combined with G⁃17 was higher than that of PGR alone, and its AUC was greater than that of PGR combined with G⁃17 and PGⅠ (P<0.05). Ultimately, based on PGR and G⁃17, the Hangzhou ABC method (PGR ≤4.98 or G⁃17 ≥9.78 pmol/L) was established. (3) Validation stage: the Hangzhou ABC method demonstrated superior sensitivity (69.23%) and AUC (0.708) for gastric cancer diagnosis compared to the new ABC method (50.77% and 0.629, respectively). Conclusion For gastric cancer screening, PGR is the single serological indicator with superior diagnostic performance, and its combination with G⁃17 further enhances diagnostic value. The Hangzhou ABC method, established using cut⁃off values adjusted for local population characteristics in the Hangzhou area, demonstrates superior screening performance as compared with the new ABC method, and is more suitable for early gastric cancer screening and risk stratification in the Hangzhou area.