Objective:To explore the screening scheme of gastric cancer in large-scale natural population in Wuxi.Methods:From December 2016 to December 2019, 105 865 residents of 19 communities (villages) in six streets of Xinwu District, Wuxi were randomly enrolled in this study by random number table. A household epidemiological questionnaire survey was conducted among 50 063 target population subjects (aged 40-69), and then, respondents were divided into four categories, category Ⅰ: HP (-), PG (-); category Ⅱ: HP (+ ), PG (-); category Ⅲ: HP (+ ), PG (+ ); category Ⅳ: HP (-), PG (+ )according to the serological Helicobacter pylori ( HP) antibodies and pepsinogen (PG) test results. People in category Ⅲ and Ⅳ were all selected into group C and group D respectively, then individuals 3 times of group D were randomly selected from category Ⅰ to assign to group A, and individuals 3 times of group C from category Ⅱwere assigned to group B in the same way. Remaining individuals in category Ⅰ and Ⅱ who had first-degree family history of gastric cancer were also included in group A and group B, respectively. Endoscopic and pathological examination were performed on the above enrolled subjects for high grade intraepithelialneoplasia (HGIN), early gastric cancer and gastric cancer. Results:Of the 50 063 target subjects, 31 508 questionnaires were finally collected, with a participation rate of 62.9%. A total of 19 745 people were tested for serology, and the participation rate was 39.4% (19 745/50 063). Serological results showed that there were 11 152 people (56.48%) in category Ⅰ, 8 170 (41.38%) in category Ⅱ, 124 (0.63%) in category Ⅲ, and 299 (1.51%) in category Ⅳ. According to the exclusion criteria and principle of voluntariness, 3 400 individuals were candidates to undergo gastroscopy. Finally, a total of 2 389 people came to the hospital for gastroscopy, 1 263 in group A, 814 in group B, 86 in group C and 226 in group D, with an overall response rate of 70.3% (2 389/3 400), target population participation rate of 4.8% (389/50 063), and the overall population participation rate of 2.3% (2 389/105 865). In the 2 389 cases, there were 32 cases (1.34%) of HGIN and gastric cancer by gastroscopy and biopsy pathology, among which 1 case (3.125%) aged 40-49, 9 (28.125%) aged 50-59, and 22 (68.750%) aged 60-69. Among the 32 cases, 25 cases (78.13%)were pathologically confirmed as having HGIN or early gastric cancer by endoscopic submucosal dissection or surgical operation. By eliminating 810 people (including 3 gastric cancer) without first-degree family history with gastric cancer in group Ⅰ and Ⅱ, and increasing the gastroscopy screening age to 50 years (exluding 214 people aged 40-49, including 1 gastric cancer), the number of people who should undergo gastroscopy could be reduced from 2 389 to 1 365, and 28 cases of HGIN or gastric cancer were still detected, including 22 HGIN or early gastric cancer.Conclusion:Gastroscopy after the screening with epidemiological, serological tests, age and first-degree relative with gastric cancer family history is suitable for gastric cancer screening in Wuxi. Based on Chinese national conditions, a new community gastric cancer screening program is recommended in Wuxi considering cost-effectiveness, which includes those over 50 years old, serological PG (+ ) and first-degree relatives with family history of gastric cancer.