Micrometer-sized single-crystalline In₂Se₃ nanosheets are synthesized by epitaxial growth from In₂Se₃nanowires. The In₂Se₃ nanosheets possess anisotropic structural configuration with intralayer covalent bonding and interlayer van der Waals bonding. Phototransistors based on the In₂Se₃ nanosheets are realized, and the devices show high photoresponsivity and high photo On/Off ratio up to two orders. The photo-gating effect can be modulated by the gate bias, indicating potential utility of the In₂Se₃ nanosheets in a variety of optoelectronic applications.