A series of organofunctional polysilsesquioxane hollow spheres were prepared by an environment-friendly method. The use of this simple and reproducible synthetic approach resulted in highly uniform and monodisperse hollow spheres with high coverage of functional groups, namely, fluoroalkyl, phenyl, vinyl and methyl groups. By adjusting the precursor concentration, the particle size and shell thickness could be precisely controlled. The structure and functionality of these hollow spheres were characterized by field-emission scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, solid-state NMR spectroscopy, X-ray diffraction and nitrogen adsorption–desorption studies. These materials were used as adsorbents to treat the benzophenone-containing wastewater, and it was found that the hydrophobic contaminants could be effectively removed. The hydrophobic surface property of the polysilsesquioxane hollow spheres was found to be an important factor that influences the adsorption capacity.