and antibiotic therapy require long-term treatment with the risk of recurrence. [2,3] Moreover, the continuous use of antibiotics can lead to the emergence of drug resistance, posing a greater challenge to modern medicine, and also laying a heavier burden to finance. [4] Hence, it is necessary to put forward alternatives to antibiotics. Fortunately, nanotechnology has provided a new opportunity to combat these problems, which is more specific, efficient, and controllable. Up to now, many researchers have focused on phototherapy, that is, irradiating material with a certain wavelength of light to bring up temperature increase or the release of reactive oxygen species (ROS) to kill target pathogens. [5] However, due to limited penetration of light, it is not suitable to cure deep-seated diseases, such as osteomyelitis. [4b,6] Ultrasound (US) is a mechanical wave with a frequency higher than 20 kHz, which has been used in clinical diagnosis. [7] Due to deeper penetration and low invasiveness, the US is considered a new kind of exogenous stimuli. [8] Hence, sonodynamic therapy (SDT) is put forward. When US is applied on aqueous solutions, gas bubbles will form, grow and collapse, which is called the "cavitation" effect. US can also arouse sonoluminescence, which further stimulates sonosensitizers to generate ROS. [7] However, SDT is still in its infancy, as sonosensitizers with appropriate US response are still in need. Up to now, noble metals, [9] piezoelectric materials, [10] porphyrin and its derivates, [11] have been used as sonosensitizers. Nevertheless, as for porphyrin and its derivates, they tend to aggregate in solutions and are easy to be metabolized, which all seriously hinder the effect of SDT. [12] To tackle this problem, porphyrins can be coordinated with metal nodes, forming a metalorganic framework (MOF). [13] Moreover, under an elaborate selection of metal nodes and design of MOF structure, MOF can be multifunctional and the US-response of porphyrin can be increased as well. To further improve the catalytic properties of MOFs, defects can be introduced into MOFs, which are sites that break the periodic arrangement of atoms or ions in the original structure. [14] However, the formation of defects in MOFs usually acquires a complex design of MOF fabrication or post-synthetic procedure such as H 2 reduction [15] and etching. [16] Precise control of defect formation is also difficult to achieve.Defect engineering is an important way to tune the catalytic properties of metal-organic framework (MOF), yet precise control of defects is difficult to achieve. Herein, a cerium-based MOF (CeTCPP) is decorated with Au nanoparticles. Under ultrasound irradiation, Au nanoparticles can precisely turn 1/3 of the pristine Ce 3+ nodes into Ce 4+ . With the stable existence of Ce 4+ , the coordination of Ce nodes changed, causing the structural irregularity in CeTCPP-Au, so that the electron-hole recombination is obviously hindered, facilitating the generation of reactive oxygen species. Therefore, under 20 min of...