Tetra(3-mercaptopropyl)-silsesquioxanes with double-decker (DDSQ) or ladder nano-cores were easily prepared from the corresponding tetraallyl derivatives through fast and convenient thiol-ene reactions. An additional tetrathiol-DDSQ with more flexible arms was also synthesized in high yield from the corresponding tetrachloro-DDSQ derivative. The three novel tetrathiol silsesquioxanes described represent versatile building blocks for the preparation of hybrid organic-inorganic materials.