Background: Alterations in IgG glycosylation have been observed in many inflammatory activities and diseases progression, uncovering IgG glycome contributes to deciphering the molecular mechanism of human diseases. Gastric cancer (GC) associated IgG glycosylation was rarely investigated.Methods: We comprehensively characterized IgG N-glycome profile in GC by high-throughput orthogonal mass spectrometry assay, and analyzed the difference of glycosylation between controls and GC patients through multiple statistical tools. Bioinformatics analysis was performed to study the candidate glycogens and their biological functions involved in GC. Results: GC associates with decrease in galactosylation and sialylation of IgG, and increase in bisection and agalactosylation of IgG.Bioinformatics analysis verified the differential expression of significantly changed IgG glycan associated glycogens, indicating the crucial role of IgG glycosylation in the pathogenesis of GC.Conclusions: This study demonstrates the potential diagnostic merits of specific IgG glycans for early detection of GC, as well as revealing molecular mechanism in the development of this cancer.