Bi₂Se₃ has been widely used as a promising photothermal and photoacoustic agent recently. Herein, two-dimensional (2D) Bi₂Se₃ nanosheets with different sizes of about 30 nm (Bi₂Se₃-30) and 80 nm (Bi₂Se₃-80) have been successfully synthesized via solution-based methods. Both of the Bi₂Se₃ nanosheets possess high near-infrared (NIR) optical absorption, efficient photothermal conversion and excellent photoacoustic behaviors. Meanwhile, the Bi₂Se₃-30 nanosheets perform better. These results indicate the smaller Bi₂Se₃ nanosheets are more promising for optical diagnostic and photothermal therapy.