Objective To compare the detection rates of early gastric cancer by different serological risk stratification methods and assess risk factors of gastric cancer in Huaibei area. Methods The patients with upper gastrointestinal symptoms in Huaibei People""s Hospital, Huaibei Miners General Hospital and Anhui Suixi Hospital were examined by serological tests, endoscopic and pathological examinations from November 2018 to June 2020. The serological tests included Helicobacter pylori (HP) antibody, pepsinogen (PG) Ⅰ, PG Ⅱ, gastrin-17 (G-17), and pepsinogen ratio (PGR, PGⅠ/PGⅡ). The consistence and detection rates of gastric cancer of serum ABC method (combination of HP antibody and PGR), new ABC method (combination of PGR and G-17) and new screening scoring system (combination of age, gender, HP antibody, PGR and G-17) were compared by using Chi-square test and Kappa consistency test. Receiver operator characteristic (ROC) curves were used to determine the thresholds of PGⅠ, PGⅡ, G-17 and PGR for gastric cancer diagnosis. Univariate and multivariate logistic regression analysis were used to screen the high-risk factors for gastric cancer. Results A total of 1 093 subjects were included, and 1 021 patients with gastric and duodenal diseases were studied. Among them, 28 cases (2.74%) were finally diagnosed as gastric cancer, including 17 (60.71%) early gastric cancer. There were 3 cases (0.49%, 3/614), 7 cases (2.32%, 7/301) and 18 cases (16.89%, 18/106) of gastric cancer in the low-risk, intermediate-risk and high-risk group of new scoring system, respectively. The detection rate of gastric cancer in the high-risk group of new scoring system was higher than that in two other groups (all P<0.001). The detection rate of gastric cancer via new screening scoring system was significantly higher than that of serum new ABC method and ABC method (Kappa=0.220, Kappa=0.185; P=0.007, P=0.049). The area under the ROC curve for diagnosis of gastric cancer by PGⅠ, G-17 and PGR were 0.651, 0.629 and 0.729, respectively. When the cut-off value of PGR<2.96, the sensitivity, specificity, positive likelihood ratio and negative likelihood ratio were 0.714, 0.768, 3.084 and 0.374, respectively. High-risk factors of gastric cancer with multivariate logistic regression analysis were family tumor history (OR=7.003, 95%CI: 2.119-23.146, P=0.001), HP infection (OR=3.556, 95%CI: 1.478-8.557, P=0.005), advanced age (OR=1.203, 95%CI: 1.138-1.272, P<0.001), and smoking (OR=1.878, 95%CI: 1.316-2.679, P=0.001）. Conclusion New scoring system has a higher predictive value than serum ABC and new ABC method for screening of early gastric cancer. And family tumor history, HP infection, advanced age, and smoking are high-risk factors for gastric cancer. Combination of both high-risk factors and new scoring system can facilitate the screening of early gastric cancer in Huaibei area.