Tetrabutyl titanate and acetic acid were used as the raw materials to synthesize TiO2 nanocrystal through a hydrothermal reaction. TiO2 nanocrystal was further reacted with Bi(NO3)3 to prepare Bi2O3/TiO2 nanoparticles (BTH). Finally, the BTH@PDA nanoparticles (BTP) were obtained by coating with a polydopamine (PDA) layer. Morphology and composition of BTP were characterized by TEM, XRD and XPS. The biosafety, biocompatibility and the ability of reactive oxygen species (ROS) generation of BTP were evaluated through biosafety test, cytotoxicity assay, cellular uptake assay and ROS staining respectively. The results indicated that BTP exhibited a fusiform shape, with the longest side having a particle size of (125.18±14.66) nm. Zeta potential of BTP was (-4.17±0.33) mV. The BTP suspension showed no obvious toxicity towards L929 and 4T1 cells at concentrations significantly above the normal treatment (300 μg/mL). Meanwhile, BTP could enhance the therapeutic outcome of radiotherapy and effectively generate ROS in response to ultrasound. After co-irradiated by ultrasound and X-ray, BTP could reduce the survival rate of 4T1 cell to 34.3%. The cellular uptake of BTP by 4T1 cells was time-dependent, with the maximum uptake occurring around 12 hours.