OBJECTIVE: To investigate the clinical value of serum autoantibodies in the screening and diagnosis of gastric cancer. MATERIALS & METHODS: A total of 570 gastric cancer patients and 373 controls were enrolled in this study. Enzyme-linked immunosorbent assay (ELISA) was employed to quantitatively detect autoantibodies in the tested serum, and statistic modeling was conducted to analyze their relationships with various clinical and pathological parameters. RESULTS: The results of autoantibody detection in gastric cancer patients were significantly different from those of the control group. A combination of 7 autoantibodies, including CLDN18, CAGE1, CTAG1A, PBRM1, RASSF7, IMMP2L and COPB1, was selected for modeling (AUC = 0.885). The diagnostic specificity was approximately 0.86 when combined 7-TAAs with Helicobacter pylori, while the positive predictive value was increased to 0.94. The abnormal elevation of different TAAs proteins in gastric cancer patients is related to factors such as disease stage, tumor differentiation degree, and invasion depth. CONCLUSION: The determination of serum autoantibody panel has clinical value in screening and prediction of gastric cancer, and can be used as an auxiliary index in clinical diagnosis. The combination of 7-TAAs and Helicobacter pylori can effectively improve the screening specificity and positive predictive value. The detection results of different proteins were related to the stage of disease, the degree of tumor differentiation and the depth of invasion.