Ultrathin TiO2-based nanosheets (TNSs) are prepared by a novel and facile hydrothermal route. It is found that TiO2 nanoparticles can be completely converted into layered titanate structure when they are first treated with high concentrated NaOH solution, which is crucial to hinder the formation of tube-like structure and facilitate the final synthesis of pure sheet-like structure. Besides, ultrathin TNSs composed of 1–3 monolayers with an interlayer spacing of ca. 1.02nm can be obtained by a further treatment of exfoliation. The prepared TNSs exhibit much higher photocatalytic activity than commercial P25 TiO2. Owing to the advantages of uniform morphology, ultrathin thickness, and high charge-separation efficiency, the obtained TNSs may have a wide application prospect in photocatalysis and some related fields.