Monodisperse yolk-shell mesoporous hybrid spheres with ordered radial mesochannels are demonstrated to be readily prepared by incubating mesostructured hybrid spheres with water. The obtained yolk-shell mesoporous spheres have inorganic-organic hybrid framework, tunable diameter, high surface area, radially oriented ordered mesochannels, large pore volume, and excellent hemocompatibilitys, showing great promise for various applications.