A highly moisture-proof polysilsesquioxane coating was obtained from a new bis-silylated precursor, which was synthesized from 3-aminopropyltriethoxysilane (APTES) and m-xylylene diisocyanate (m-XDI) in tetrahydrofuran (THF) and verified by 1H MAS NMR. For direct comparison purposes, an SiO2 coating was also prepared by the St梥r method using tetraethoxysilane (TEOS) as the reactant. Interestingly, the coating obtained from the polysilsesquioxane sol exhibited a much higher moisture resistance capability than its counterpart, which was attributed to its more compact feature between nanoparticles as characterized by N2 absorption experiment and transmission electron microscopy (TEM). Furthermore, its high transparency of about 92% showed potential for application in the protection of optical crystals.