Owing to wide-ranging industrial applications and fundamental importance, tailored synthesis of well-faceted single crystals of anatase TiO2 with high percentage of reactive facets has attracted much research interest. In this work, high-quality anatase TiO2 single-crystal nanosheets mainly dominated by {001} facets have been prepared by using a water−2-propanol solvothermal synthetic route. The synergistic functions of 2-propanol and HF on the growth of anatase TiO2 single-crystal nanosheets were studied by first-principle theoretical calculations, revealing that the addition of 2-propanol can strengthen the stabilization effect associated with fluorine adsorption over (001) surface and thus stimulate its preferred growth. By measuring the •OH species with terephthalic acid scavenger, the as-prepared anatase TiO2 single-crystal nanosheets having 64% {001} facets show superior photoreactivity (more than 5 times), compared to P25 as a benchmarking material.