This study constructed a model for the early diagnosis of gastric cancer by comparing the serum peptides profiles of patients with advanced gastric cancer and healthy people. And that model may be the potential to be applied for the efficacy evaluation and recurrence monitoring in gastric cancer. Serums of 30 healthy people and 30 advanced gastric cancer patients were matched by age and gender were collected. The serum peptide spectrum was obtained by MB-WCX concentration and MALDI-TOF MS analysis. Based on the analysis of the efficiency of differential peptides in the diagnosis of gastric cancer, we first established a model for the diagnosis of gastric cancer based on differential peptides and then carried out external verification. The diagnostic reliability of this model was further tested by compared with carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). In this present study, we found the expression of two peptide peaks with a molecular weight of 2863 Da and 2953 Da were significantly increased in gastric cancer serum, while the expression of two peptide peaks with a molecular weight of 1945 Da and 2082 Da were significantly decreased. Depending on the characteristics of peptide expression, we constructed a diagnostic model, we compared the sensitivity and specificity of the model established by 2953 Da/1945 Da, and found this model is significantly higher than CEA and CA19-9. There were some differences in serum peptides profiles between patients with advanced gastric cancer and healthy people. The serum peptide diagnostic models based on 2953 Da and 1945 Da have high diagnostic efficiency for advanced gastric cancer. Our result indicated that this model was well worth further validation for clinical diagnosis. Copyright © 2020 Ning Zhu et al.