Mesoporous TiO2 has several potential applications due to its unique electronic and optical properties, although its structures and morphologies are typically difficult to tune because of its uncontrollable and fast sol-gel reaction. In this study we have coupled the template-directed-sol-gel-chemistry with the low-cost, scalable, and environmentally benign aerosol (spray-drying) one-pot preparation technique for the fabrication of hierarchically mesoporous TiO2 microspheres and Fe3O4@mesoporous TiO2-x micro spheres in a large scale. Parameters during the pre-hydrolysis and spray-drying treatment were varied to successfully control the bead diameter, morphology, monodispersity, surface area and pore size for improving their effectiveness for better application. Unlike to the previous aerosol synthetic approaches, where mainly quite a high temperature gradient with the strict control of spray-drying precursor concentration is implied, our strategy is lying on comparatively low drying temperature with an additional post-ultrasonication (further hydrolysis and condensation) route of the pre -calcined TiO2 samples. As -synthesized mesoporous microspheres have a size distribution from 500 nm to 5 mu m, specific surface areas ranging from 150 to 162 m(2) g(-1) and mean pore sizes of several nanometers (4-6 nm). Further Fe3O4@mesoporous TiO2-x microspheres were observed to show remarkable selective phosphopeptideenrichment activity which might have significant importance in disease diagnosis and other biomedical applications. (C) 2016 Published by Elsevier Inc.