We developed a facile one-pot method to synthesize multishelled hollow mesoporous SiO2 microspheres (HMSs) with controllable interior structures including one-shell, double-shell, and yolk-shell. Single reagent formaldehyde could fully control the morphology of HMSs, in that formaldehyde was crucial to the SiO2 precursor's hydrolysis rate and the template pore size.