A substrate-independent fabrication of hollow sphere arrays on desired substrates were demonstrated based on sulfonated polystyrene sphere template-assisted hydrothermal approach. By using this approach, Fe2O3 mono/multilayer hollow sphere arrays with tunable shell thickness and sphere diameter have been successfully prepared. Specially, this approach is universal for many other materials, such as the metal oxide In2O3, NiO, Co3O4, MgO, ZnO, CuO and SnO2, and the organic semiconductor polyaniline. Moreover, we can control the deposition of these hollow sphere arrays on any desired substrate such as flexible, glass slide, silicon wafer and flat plate electrode, which is very important for their applications in many fields, such as gas sensing. As an example, the Fe2O3 monolayer hollow sphere array as gas sensor was investigated in detail. It was found that the Fe2O3 hollow sphere arrays-based sensor display enhanced sensing performances with easy controllability, nice repeatability, high sensitivity, high stability and high selectivity in certain conditions, superior to those prepared by other methods, such as brushing. Generally, the proposed template-assisted hydrothermal approach afforded a new facile and universal approach to fabricate mono/multilayer hollow sphere arrays on any substrate, which will show high advantages in applications due to the controllable in-situ growth of the materials on desired devices.