Organic-inorganic hybrid particles have many potential applications, but almost all of this research was focused on the hybrid particles containing one kind of inorganic nanoparticles. This paper presented a facile preparation method for SiO2/PS/TiO2 multilayer core-shell hybrid microspheres. In this approach, positively charged SiO2/PS core-shell hybrid particles were first synthesized by miniemulsion polymerization using cationic initiator and emulsifier. These positively charged SiO2/PS hybrid particles were mixed with tetra-n-butyl titanate for sol-gel reaction to directly form SiO2/PS/TiO2 multilayer core-shell hybrid microspheres. Some influencing parameters such as surfactant concentration, tetra-n-butyl titanate amount, and glacial acetic acid amount were investigated. TEM, TGA, and EDX analyses indicated that titania layers were successfully coated onto the surfaces of hybrid microspheres.