Abstract: OBJECTIVE To evaluate the influencing factors of hospital-associated infection in patients undergoing craniocerebral surgery, and to provide evidence for optimizing infection prevention and control strategies. METHODS A retrospective case-control study was conducted, including 4 048 patients who underwent craniocerebral surgery and were admitted to three tertiary general hospitals from Jan. 2016 to Dec. 2022. Patients were divided into an infection group (n=365) and a non-infection group (n=3 683) based on whether they developed hospital-associated infections. Clinical data and other relevant information were retrospectively collected from the hospital information system. Chi-square test and logistic regression were used to analyze the factors associated with postoperative infections. RESULTS This study included a total of 4 048 patients who underwent craniocerebral surgery, with a hospital-associated infection rate of 9.02% after craniocerebral surgery. The average length of hospital stay in the infection group was 14.91 days longer than that in the non-infection group. Influencing factors for infections after craniocerebral surgery included being aged ≥60 years, being male, having a history of heart disease, previous craniocerebral surgery, National Nosocomial Infection Surveillance(NNIS) score ≥2, preoperative use of antib, use of ventilators, central venous catheterization, urethral catheterization, and emergency surgery (P<0.05). CONCLUSIONS Hospital-associated infection after craniocerebral surgery is a complex process involving multiple factors. Clinically, it is necessary to implement a hierarchical prevention and control strategy based on risk assessment, targeting its influencing factors, in order to minimize the incidence of infection and improve the prognosis of patients.