The inherent radioresistance and inaccuracy of localization of tumors weaken the clinical implementation effectiveness of radiotherapy. To overcome these limitations, hyaluronic acid-functionalized bismuth oxide nanoparticles (HA-Bi
2
O
3
NPs) were synthesized by one-pot hydrothermal method for target-specific computed tomography (CT) imaging and radiosensitization of tumor. After functionalization with hyaluronic acid, the Bi
2
O
3
NPs possessed favorable solubility in water and excellent biocompatibility and were uptaken specifically by cancer cells overexpressing CD44 receptors. The as-prepared HA-Bi
2
O
3
NPs exhibited high X-ray attenuation efficiency and ideal radiosensitivity via synergizing X-rays to induce cell apoptosis and arrest the cell cycle in a dose-dependent manner in vitro. Remarkably, these properties offered excellent performance in active-targeting CT imaging and enhancement of radiosensitivity for inhibition of tumor growth. These findings demonstrated that HA-Bi
2
O
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NPs as theranostic agents exhibit great promise for CT imaging-guided radiotherapy in diagnosis and treatment of tumors.
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