Although efforts have been devoted to develop new antibacterial agents and techniques, the challenge of bacterial infection remains unresolved and is even increasing. Sonodynamic therapy (SDT) driven by ultrasound (US) has demonstrated effectiveness in terms of penetration and it can help to clinically address the problem of deep tissue bacterial infection. In recent years, a variety of sonosensitizers, which were originally designed for photodynamic therapy, have been adopted for SDT. Yet, their unstable chemical stability and ineffective electron-hole separation are not favorable for clinical applications. Hence, we designed a new type of antibacterial sonosensitizer-namely, Au@Cu2O hybrid nanocubes-in which an interfacial Schottky junction was built between a p-type semiconductor Cu2O and a noble metal Au. When US stimulation was applied, the electrons from Cu2O could be excited at the junction and transferred to Au. Since the formed Schottky barrier could block the backflow of US-excited electrons, a prolonged electron-hole separation can be successfully established. Additionally, because of the boosted sonocatalytic activity, the Au@Cu2O hybrid nanocubes could produce a large amount of reactive oxygen species (ROS), which are subject to US stimulation. Furthermore, we found that the sonocatalytic activity of the Au@Cu2O hybrid nanocubes could be reinforced by increasing the amount of Au, enabling 99.67% of Staphylococcus aureus (S. aureus) to be killed by US stimulation for 15 minutes. The cytocompatibility of Au@Cu2O hybrid nanocubes was improved by a red blood cell membrane (RBC) coating over the surface, and the membrane did not sacrifice its superior antibacterial properties.