The invention relates to the field of 
polymer material and analysis, and relates to organic-inorganic 
hybrid core-shell-structured 
microsphere particles, and a preparation and an application thereof. According to the invention, inorganic 
silica gel particles are adopted as cores, and are modified with a 
silanization agent; with a 
thiol-ene 
click chemistry technology, 3-allyloxy-2-hydroxy-1-propanesulfonic acid and 
methylene diacrylamide are wrapped on the surfaces of the cores, such that the organic-inorganic 
hybrid core-shell-structured nano / 
micro particles with 
smooth surface and with hydrophilic functional groups such as hydroxyl group, 
sulfonic acid group, 
amide and the like are formed. According to the invention, the hydrophilic functional groups such as hydroxyl group, 
sulfonic acid group, 
amide and the like are introduced to the surface of the material through the 
thiol-ene method, such that the defects of complicated steps and low reaction efficiency of a traditional post-modification method are solved, and a 
polymer three-dimensional-structured hydrophilic layer is formed. Better 
advantage is shown when the particles are used in hydrophilic 
chromatography. The 
microsphere particles can be used in 
hydrophilic interaction chromatography for separating and enriching 
glycopeptide, and have good practical value and application prospect in the fields of separation analysis and 
sugar proteomics.