Objective To investigate the causes of the outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection in the neurological intensive care unit (ICU), and provide evidence for effective control of multidrug-resistant organism healthcare-associated infection (HAI). Methods An on-site epidemiological investigation and environmental hygiene monitoring were conducted on patients with CRKP infection in the neurological ICU of a hospital from June to July 2021. Control measures were taken, and the effectiveness of prevention and control mea-sures was evaluated. Results There were 7 cases of CRKP HAI cases, with an incidence of 12.28% (7/57), which was significantly different from the incidence during the same period in 2019 and 2020 (P < 0.05). Environmental hygiene monitoring showed that the isolation rate of CRKP from hand specimens was 6.67% (1/15), which was from the hand of a cleaner. Isolation rate of CRKP from environmental object surface was 5.45% (3/55), which were from bedside table and infusion pump of bed-19, as well as personal digital assistant-1(PDA-1). After taking a series of targeted measures such as centralized isolation of CRKP-infected patients, strict restriction on personnel movement, ward cleaning and disinfection, and strengthening hand hygiene supervision, the outbreak has been effectively controlled. Conclusion This event is considered as a suspected outbreak of CRKP HAI. It is speculated that the main causes for this outbreak were the failure to adopt centralized isolation measures for CRKP-infected patients, incomplete environmental disinfection, and poor execution of hand hygiene. Early identification of infection outbreak, investigation of causes, and timely adoption of effective targeted measures are key to controlling infection outbreaks.