A versatile targeted etching strategy is developed for the large-scale synthesis of urchin-like mesoporous TiO2 hollow spheres (UMTHS) with tunable particle size. Its key feature is the use of a low-temperature hydrothermal reaction of surface-fluorinated, amorphous, hydrous TiO2 solid spheres (AHTSS) under the protection of a polyvinylpyrrolidone (PVP) coating. With the confinement of PVP and water penetration, the highly porous AHTSS are selectively etched and hollowed by fluoride without destroying their spherical morphology. Meanwhile TiO2 hydrates are gradually crystallized and their growth is preferentially along anatase (101) planes, reconstructing an urchin-like shell consisting of numerous radially arranged single-crystal anatase nanothorns. Complex hollow structures, such as core–shell and yolk–shell structures, can also be easily synthesized via additional protection of the interior by pre-filling AHTSS with polyethylene glycol (PEG). The hollowing transformation is elucidated by the synergetic effect of etching, PVP coating, low hydrothermal reaction temperature, and the unique microstructure of AHTSS. The synthesized UMTHS with a large surface area of up to 128.6 m2 g-1 show excellent light-harvesting properties and present superior performances in photocatalytic removal of gaseous nitric oxide (NO) and photoelectrochemical solar energy conversion as photoanodes for dye-sensitized mesoscopic solar cells.