Staphylococcus aureus (S. aureus) is the most common pathogen in human purulent infections, which can cause local purulent infections, as well as pneumonia, pseudomembranous enteritis, pericarditis, and even systemic infections. The conventional methods including bacteria colony counting, polymerase chain reaction and enzyme-linked immunosorbent assay can't fully meet the requirement of highly sensitive detection of S. aureus due to their own disadvantages. Therefore, it's an urgent need to develop new platform to detect S. aureus in the early infection stage. In this study, a new surface-enhanced Raman scattering (SERS)-based nanoplatform based on dual-recognition of aptamer (Apt) and vancomycin (Van) was developed for the highly sensitive detection of S. aureus. The SERS nanoplatform consisted of two functional parts: aptamer-conjugated Fe