Objective To evaluate the risk factors and transmission routes of a cluster of surgical site infection (SSI) in the department of thyroid surgery in a hospital, and provide reference and basis for formulating prevention and control strategies. Methods An epidemiological investigation on SSI cases in the wards of thyroid disease from April to May 2025 was conducted. High-risk factors for infection were analyzed using the case-control method. Environmental hygiene detection was conducted. Intervention measures were implemented and their effectiveness was evaluated. Results Staphylococcus aureus with identical drug susceptibility profiles were detected from wound secretion or drainage fluids of 4 SSI patients. Tracing survey revealed that multiple healthcare workers (e.g., B2, B3) and frequently touched environmental surfaces carried highly consistent methicillin-resistance Staphylococcus aureus (MRSA) strains. It was thus inferred that the transmission was due to healthcare workers carrying MRSA, which contaminated the environment and led to infection through contact transmission. By adjusting the decolonization strategies and performing effective decolonization for colonized patients using mupirocin ointment, along with a series of measures such as strict environmental disinfection and hand hygiene, there was no new SSI cases occurred in the ward, indicating the effectiveness of the infection control measures. Conclusion The colonization with Staphylococcus aureus in healthcare workers can increase the risk of SSI in patients. Therefore, it is recommended to conduct regular active screening and decolonization interventions for surgeons involved in specific surgeries to reduce the incidence of SSI.