Osteosarcoma (OS) is the most normally primary malignant bone cancer in adolescents. Due to their analogous X-ray attenuation properties, healthy bones and malignancies with iodine enhancement cannot be distinguished by conventional computed tomography (CT). As one kind of spectral CT, dual-energy CT (DECT) offers multiple functions for material separation and cancer treatments. Herein, bismuth sulfide (Bi₂S₃) nanorods (NRs) were synthesized as special contrast agents (CAs) for DECT, which have superior imaging properties than clinical iodine CAs. At the same time, the high photothermal conversion rates of Bi₂S₃ NRs can be used for DECT-guided photothermal therapy (PTT) to destroy OS and inhibit tumor growth under the guidance of DECT imaging. Importantly, DECT imaging real-timely monitored that PTT could accelerate the diffusion of Bi₂S₃ NRs in the tumor, obtaining detailed information on the internal distribution of nanomaterials in tumors around the bone to avoid injury to normal tissues by PTT. Overall, the proposed strategy of DECT imaging-guided PTT appears enormous promise for bone disease treatment.