Abstract: Objective To investigate the changes and clinical significance of cerebrospinal fluid heparin binding protein(HBP) in patients with secondary intracranial infection after craniocerebral surgery. Methods A total of 61 patients with intracranial infection after craniocerebral surgery in the First Affiliated Hospital of Bengbu Medical College from January 2019 to June 2020 were enrolled. According to the outcome after treatment, they were divided into cured group(42 cases) and unhealed group(19 cases). The body temperature, Glasgow score(GCS score), white blood cell(WBC) counts, lactic acid(Lac) and HBP levels in cerebrospinal fluid and the levels of WBC and HBP in serum were compared before and after anti-infection treatment. The ROC curve was drawn to calculate the specificity and sensitivity of the indicators with statistical significance. The significance of each index in predicting the severity of infection and prognosis during treatment was analyzed and compared. Results Before treatment, the cerebrospinal fluid lactic acid and HBP levels of the unhealed group were significantly higher than those of the cured group(all P<0.05), and there was no statistical difference in the other indicators. After 7 days of treatment, the body temperature, GCS, cerebrospinal fluid WBC, Lac and HBP were significantly higher than the cured group(all P<0.05). After treatment, the area under the ROC curve of cerebrospinal fluid HBP was 0.930, and its specificity and sensitivity were 0.976 and 0.895, respectively. The area under the ROC curve of cerebrospinal fluid Lac was 0.650, and its specificity and the sensitivity was 0.833 and 0.579, respectively. The area under the ROC curve of cerebrospinal fluid WBC was 0.702, and its specificity and sensitivity were 0.140 and 0.737, respectively. There was no statistical difference in serum WBC and HBP between the two groups before and after treatment. Conclusion The changes in cerebrospinal fluid HBP levels after treatment have clinical significance in the evaluation of the severity and prognosis of patients with intracranial infections after craniocerebral surgery. Compared with traditional indicators such as cerebrospinal fluid WBC, the change of cerebrospinal fluid HBP level can better reflect the condition and predict the prognosis, which is conducive to timely assessment of the condition and improvement of clinical treatment effects.