Objective To analyze the incidence and risk factors of surgical site infection (SSI) after clean incision craniotomy of neurosurgery, and provide basis for prevention and control of SSI. Methods From July 2017 to December 2018, patients with clean incision craniotomy in department of neurosurgery of a tertiary general hospital were prospectively monitored for SSI, occurrence of SSI was monitored, univariate analysis and multivariate logistic regression analysis were used to analyze the influencing factors for SSI in clean incision craniotomy. Results Among 1 154 patients who underwent clean incision craniotomy, 105 (9.10%) had SSI, 11 were superficial incision infection and 94 were organ space infection, there was no deep incision infection. Multivariate logistic regression analysis showed that reoperation, duration of postoperative drainage ≥ 4 days, duration of operation ≥ 4 hours and emergency operation were independent risk factors for SSI in clean incision craniotomy. Postoperative epidural/subdural drai-nage (no more than 72 hours) was a protective factor for SSI in clean incision craniotomy. 87.62% (92/105) of patients developed SSI within 2 weeks after surgery. Conclusion In order to reduce the occurrence of SSI of clean incision craniotomy of neurosurgery, it is necessary to avoid reoperation, shorten operation time, strengthen mana-gement of emergency operation and place epidural/subdural drainage if necessary, but drainage tube should be removed as early as possible.