Bi, a high atomic number element, has a high photoelectric absorption coefficient, and Se has anticancer activity. Hence, their compound chalcogenide (Bi₂Se₃) deserves a thorough investigation for biomedical applications. This study reveals that Bi₂Se₃ nanoplates (54 nm wide) protected with poly(vinylpyrollidone) (PVP) could be presumed to have low toxicity even at a high dose of 20 mg/kg in mice. This conclusion is made through studies on the biodistribution and 90‐day long term in vivo clearance of the nanoplates. The liver and spleen are dominant organs for accumulation of the nanoplates, which is mainly due to RES absorption. 93% of the nanoplates are cleared after 90 days of treatment. Concentrations of Bi and Se in tumor tissue continuously increased until 72 h after intraperitoneal injection into mice. Such selective accumulation of Bi is utilized to enhance the contrast of X‐ray computerized tomography (CT) images. Bi element concentrated in a tumor leads to damage on the tumor cells when exposed to gamma radiation. Growth of the tumor is significantly delayed and stopped in 16 days after the tumor is treated by radiation with Bi₂Se₃ nanoplates. This work clearly shows that Bi₂Se₃ nanoplates may be used for cancer radiation therapy and CT imaging. The nanoplates deserve further study for biological and medical applications.