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.