Objective To investigate risk factors for the occurrence of an outbreak of surgical site infection (SSI) in the orthopedic department of a hospital. Methods Patients with SSI in the orthopedic department of a hospital in June-July 2017 were investigated, and the high-risk factors for infection were analyzed through case-control study. Specimens were taken from patients, health care workers (HCWs), environment and surgical devices for microbial detection. The homology between patients’ and environmental isolates was analyze by pulsed-field gel electrophoresis (PFGE). Results Staphylococcus aureus (S. aureus) were isolated from nasal secretion of four HCWs, including one doctor (D1) who was also isolated S. aureus from his forehead and hands. PFGE analysis found that S. aureus isolated from incision secretion of 2 patients were homologous to S. aureus isolated from the nasal cavity, forehead, and hands of doctor D1. Several targeted comprehensive infection control measures were implemented, including suspending sterile manipulation (such as surgery and dressing changes) of doctor D1; decolonization for all HCWs (including doctor D1) who carried S. aureus, requiring doctor D1 regularly trim nasal hair; strengthening the education and supervision of sterile manipulation and hand hygiene; implementing centralized isolation for SSI patients, et al. After timely implementation of the above comprehensive intervention measures, this SSI outbreak was effectively controlled in a short period of time. Conclusion Colonization of S. aureus in surgeons may lead to SSI in patients, regular active screening and decolonization of surgeons involved in specific surgeries can be considered, and if necessary, nasal colonized people with dense nasal hair are required to regularly trim their nasal hair to reduce the occurrence of SSI.