Novel sulfur-containing silsesquioxane nanoparticles, (RS–SiO1.5)n, having uniform size distribution, good solubility, and relatively high refractive index were synthesized by hydrolytic condensation of a triethoxysilane precursor derived from glycidol, followed by the esterification with sulfur-containing acid chlorides. Esterification of the water-soluble silsesquioxane nanoparticles with 3-(methylthio)propionyl chloride afforded silsesquioxane hybrid with a high density of chemically bonded peripheral methyl thioether groups, which was characterized by 1H, 13C NMR, Fourier transform infrared spectroscopy, and thermogravimetric analysis measurements. The resulting product was soluble in various organic solvents, such as CHCl3, acetone, tetrahydrofuran, dimethyl formamide, and dimethyl sulfoxide. The size of the sulfur-containing nanoparticles evaluated by X-ray diffraction was 2.1 nm. Transmission electron microscopy, gel permeation chromatography, and dynamic light scattering measurements indicated the formation of the nanoparticles having relatively narrow size distribution with an average particle diameter of less than 3 nm without aggregation. The sulfur content of the methyl thioether-containing silsesquioxane hybrid analyzed by elemental analysis was 16.1 %, which led to relatively high refractive index (nD = 1.588) and high Abbe number (34.4). Two sulfur-containing silsesquioxane hybrids with peripheral thiophene and phenyl thioether moieties were also obtained by the same procedure, and resulting hybrids showed high refractive indices of 1.605 and 1.627, and Abbe numbers of 31.8 and 24.3, respectively.