Objective To investigate the efficacy and safety of lumbar cistern drainage combined with intrathecal injection in treating intracranial infection with Acinetobacter baumannii. Methods A retrospective analysis was performed on the clinical data of 26 patients with intracranial infection with extensively drug-resistant A. baumannii who were admitted to the Neurosurgery Department of our hospital from April 2018 to December 2019. All patients were treated with lumbar cistern drainage combined with intrathecal injection of antibiotics. The changes in indicators of intracranial infection, including body temperature, neck stiffness, blood routine parameters, cerebrospinal fluid routine and biochemical parameters, and bacterial culture results of cerebrospinal fluid, were observed and recorded. The therapeutic methods were recorded, and the therapeutic efficacy was analyzed. Results Twenty-four patients were given lumbar cistern drainage alone, and the other two underwent a replacement of lumbar cistern drainage tube and were given lateral ventricular drainage additionally due to obstruction of the lumbar cistern drainage tube. Twenty-three patients were cured within 10-34 days of treatment (cure rate 88.46%), and the other three died (mortality rate 11.54%). The death time of the three patients was 4 days, 7 days and 12 days, respectively, after the confirmation of intracranial infection. Conclusions Lumbar cistern drainage combined with intrathecal injection is safe and effective in treating patients with intracranial infection with extensively drug-resistant A. baumannii, which holds promise for clinical application. If the high protein concentration in the cerebrospinal fluid causes obstruction of the lumbar cistern drainage tube, lateral ventricular drainage can be given additionally, and the tigecycline solution can be continuously irrigated from the lumbar cistern drainage tube to the lateral ventricular drainage tube.