Mesoporous nanocrystal clusters of anatase TiO2 with large surface area and enhanced photocatalytic activity have been successfully synthesized. The synthesis involves the self-assembly of hydrophobic TiO2 nanocrystals into submicron clusters, coating of these clusters with a silica layer, thermal treatment to remove organic ligands and improve the crystallinity of the clusters, and finally removing silica to expose the mesoporous catalysts. With the help of the silica coating, the clusters not only maintain their small grain size but also keep their mesoporous structure after calcination at high temperatures (with BET surface area as high as 277 m2/g). The etching of SiO2 also results in the clusters having high dispersity in water. We have been able to identify the optimal calcination temperature to produce TiO2 nanocrystal clusters that possess both high crystallinity and large surface area, and therefore show excellent catalytic efficiency in the decomposition of organic molecules under illumination by UV light. Convenient doping with nitrogen converts these nanocrystal clusters into active photocatalysts in both visible light and natural sunlight. The strategy of forming well-defined mesoporous clusters using nanocrystals promises a versatile and useful method for designing photocatalysts with enhanced activity and stability.