An interfacial sol-gel synthesis of inorganic hollow microspheres in room-temperature ionic liquids is newly developed. When metal alkoxides such as titanium tetrabutoxide, Ti(OBu)4, are dissolved in anhydrous toluene and injected into 1-buthyl-3-methylimidazolium hexafluorophosphate ([C4mim]PF6) under vigorous stirring, hollow titania microspheres are formed. The present technique is widely applicable to the reactive metal alkoxides such as Zr(OBu)4, Hf(OBu)4, Nb(OBu)4, and InSn3(OR)x, giving a general route to the metal oxide microspheres. When gold nanoparicles and carboxylate-containing dyes such as fluorescein isothiocyanate (FITC) are dissolved in the toluene microdroplets, they are stably immobilized in the microsphere shells. Calcination of the titania gel microspheres gives anatase TiO2 microspheres. The present method provides the first example of inorganic hollow microspheres formed in ionic liquids, and the ability to modify microspheres with metal nanoparticles or functional organic molecules would be widely applied to the design of smart organic/inorganic hybrid materials.