Different (3-mercaptopropyl)trimethoxysilane (MPTS) loadings of sulfonic acid-functionalized micro-bead silica (SA-SiO2) were prepared by silylation and oxidation, and characterized by elemental analysis, SEM, FT-IR, TGA, NH3-TPD, BET N2 adsorption–desorption and 13C NMR CP/MAS. The as-prepared SA-SiO2 showed strong hydrophilic nature and excellent catalytic performance for dehydration of sorbitol to isosorbide. The selectivity to isosorbide is obviously affected by the MPTS loading. Using SA-SiO2 as a solid catalyst with 60.5% MPTS loading, 100% sorbitol conversion and 84% yield of isosorbide are achieved at 120 °C for 10 h under vacuum. The catalyst was reused 10 times without noticeable loss of activity and selectivity.