The inadequate generation of reactive oxygen species (ROS) and metastasis of malignant tumors are critical factors that limit the efficacy of conventional sonodynamic therapy in cancer treatment. Herein, an engineered piezocatalyst: cholesterol oxidase (CHO)-loaded Pt-ZnO nanoparticles (Pt-ZnO/CHO) that can explosively generate large amounts of ROS and block the metastasis of tumor, is developed for improving piezocatalytic tumor therapy. In this process, Pt-ZnO can substantially generate ROS via initiating ultrasound (US)-triggered piezocatalytic reactions. In situ-grown Pt nanoparticles not only optimize piezocatalytic activities but also facilitate oxygen (O