Objective Here, Our study aimed to find the plasma biomarkers related to the diagnosis of multiple sclerosis (MS) through Liquid chromatography Mass Spectrometry (LC/MS) technology. Methods Tandem mass tag (TMT) quantitative LC/MS proteomics method was used to determine the differentially expressed proteins (DEPs) in the plasma samples of 22 MS patients and 22 healthy controls. and the functional annotations of the DEPs were analyzed by GO and IPA. The candidate protein was validated by ELISA. The receiver operating characteristic (ROC) curves were used to determine the predictive potential of the biomarker. Results LC/MS analysis of plasma proteomic identified 88 DEPs among the quantified 375 proteins, of which 39 proteins were up-regulated and 49 proteins were down-regulated. These proteins are involved in immunity/inflammation and Neurological diseases related pathways. A protein panel consisting of Alpha-1-antitrypsin (SERPINA1) and Protein S100-A9 (S100A9) were with an area under the curve (AUC) of 0.991. A MS treatment related protein, DPP4, was validated by ELISA. Conclusion DEPs related to MS can be found in the plasma proteome, which may become biomarkers for MS diagnosis. Our study layed the foundation for the further application plasma proteomics in the diagnosis of MS.