Silica nanorattles(SNs) with zinc oxide(ZnO) combination nanoparticles are reported to inhibit methicillin-resistant Staphylococcus aureus(MRSA) for the first time. SNs loaded with ZnO nanoparticles,which can produce free radicals, can cause severe damage to bacteria. ZnO nanoparticles not only provide free radicals in the combined nanostructures, which can inhibit the growth of bacteria, but also form nanorough surfaces with an irregular distribution of spikes on the SNs, which can enhance their adhesion to bacteria. Nanorough silica shell surfaces maintain the high activity and stability of small-sized ZnO nanoparticles and gather ZnO nanoparticles together to enhance production, which improves the efficiency of free radicals against the cytomembranes of bacterial cells. The enhanced adhesion of ZnO@SN nanoparticles to MRSA cells shortens the effective touching distance between free radicals and MRSA, which also improves antibacterial activity. As we expected, the ZnO@SN nanoparticles exhibit a better antibacterial effect than free ZnO nanoparticles against MRSA in vitro and in vivo. We also demonstrate that SNs loaded with ZnO nanoparticles can accelerate wound healing in MRSA skin inflammation models. This method of multilevel functionalization will be potentially applicable to the antibacterial field. Silica nanorattles (SNs) with zinc oxide (ZnO) combination nanoparticles are reported to inhibit methicillin-resistant Staphylococcus aureus (MRSA) for the first time. SNs loaded with ZnO nanoparticles, which can produce free radicals, can cause free damage to bacteria. nanoparticles not only provide free radicals in the combined nanostructures, which can inhibit the growth of bacteria, but also form nanorough surfaces with an irregular distribution of spikes on the SNs, which can enhance their adhesion to bacteria. and stability of small-sized ZnO nanoparticles and gather ZnO nanoparticles together to enhance production, which improves the efficiency of free radicals against the cytomembranes of bacterial cells. The enhanced adhesion of ZnO @ SN nanoparticles to MRSA cells shortens the effective touching distance between free radicals and MRSA, which also improves antibacterial activity. As we expected, the ZnO @ SN nanoparticle s exhibit a better antibacterial effect than free ZnO nanoparticles against MRSA in vitro and in vivo. We also demonstrate that SNs loaded with ZnO nanoparticles can accelerate wound healing in MRSA skin inflammation models. This method of multilevel functionalization will be potentially applicable to the antibacterial field .