Abstract Metal hydrides have been rarely used in biomedicine. Herein, we fabricate titanium hydride (TiH 1.924 ) nanodots from its powder form via the liquid-phase exfoliation, and apply these metal hydride nanodots for effective cancer treatment. The liquid-phase exfoliation is an effective method to synthesize these metal hydride nanomaterials, and its efficiency is determined by the matching of surface energy between the solvent and the metal hydrides. The obtained TiH 1.924 nanodots can produce reactive oxygen species (ROS) under ultrasound, presenting a highly efficient sono-sensitizing effect. Meanwhile, TiH 1.924 nanodots with strong near-infrared (NIR) absorbance can serve as a robust photothermal agent. By using the mild photothermal effect to enhance intra-tumoral blood flow and improve tumor oxygenation, a remarkable synergistic therapeutic effect is achieved in the combined photothermal-sonodynamic therapy. Importantly, most of these TiH 1.924 nanodots can be cleared out from the body. This work presents the promises of functional metal hydride nanomaterials for biomedical applications.