This study aims to investigate proteomic profiling of submandibular glands (SMGs) in IgG4 related disease (IgG4-RD). Methods: SMGs of four patients with IgG4-RD and four patients with chronic nonspecific sialadenitis were obtained for isobaric tags for relative and absolute quantitation (iTRAQ) analysis. Differentially expressed proteins (DEPs) were defined as IgG4-RD/control >1.5 or <0.67. Gene ontology (GO) analysis, protein-protein interaction network analysis, pathway and disease correlation analysis were performed. In addition, Immunohistochemistry (IHC) and enzyme linked immunosorbent assay (ELISA) were used to verify the expression levels of DEPs of interest.