Porous titanium dioxide (TiO2) microspheres (MS) were prepared by a facile ultrasonic spray pyrolysis process with commercial colloidal silica as a sacrificial template. The morphology structure, Brunauer–Emmett–Teller surface areas and pore size distribution of TiO2 microspheres were studied by changing the content and diameter of the silica template in detail. These porous micro-sized MS are composed of anatase TiO2 nanocrystallites of 5–10 nm and have unique bimodal mesopores. The largest specific surface area of 112.3 m2/g has been achieved using 60 wt% 20 nm silica as a template. When used as photocatalysts, the best photocatalytic activity of the as-prepared porous MS is comparable to commercial P25 nanopowders. Moreover, the micro-size and tailored properties from the design that appear during the ultrasonic spray pyrolysis process give these porous MS a promising application in photocatalytic reaction.