Hierarchical structure TiO2 hollow spheres composed of nanometer-sized building blocks, nanoflakes with exposed anatase (001) facets, have been synthesized with a high yield through a facile fluoride-mediated hydrothermal route. The average diameter of the resultant TiO2 hollow spheres is ∼1 μm, and the width of well-crystallized anatase phase nanoflakes is ∼50 nm. Nitrogen adsorption–desorption measurement revealed that the products have a high specific surface area of 26 m2 g−1 and abundant mesoporous structure. The TiO2 hollow spheres were used to photocatalytically degrade Cr(VI) in solution. The results indicate an enhanced photocatalytic activity compared to other TiO2 structures, owing to the high specific surface area and abundant mesoporous properties of the TiO2 hollow spheres. Besides, the presence of the reactive (001) facets also contributed to the enhanced activity; it was found that the (001) facets are more effective in the adsorption of Cr(VI) than the commonly exposed (101) facets. Furthermore, the surface fluorination of TiO2 hollow spheres was found to have a negative role in the photocatalytic removal of Cr(VI). The TiO2 hollow spheres not only can remove Cr(VI) from wastewater; they also can reduce the adsorbed toxic Cr(VI) to Cr(III), further forming oxides or hydroxides. In addition, the TiO2 hollow sphere photocatalysts with micron-scale size showed high durability in the cyclic tests.