Objective To investigate the causes for the outbreak of healthcare-associated infection (HAI) with carbapenem-resistant Klebsiella pneumoniae (CRKP) in neurosurgical intensive care unit (NSICU), identify the infection sources and transmission routes, and provide basis for the effective control of HAI with multidrug-resistant organism. Methods Epidemiological investigation was conducted on 3 patients with CRKP infection in the NSICU of a hospital from July 28 to August 2, 2023. Specimens were taken according to environmental hygienic monitoring methods. CRKP in the environment of the ward was searched. Antimicrobial resistance and resistance genes carried by CRKP strains were analyzed. The homology between CRKP strains isolated from patients and environment was analyzed by enterobacterial repetitive intergenic consensus (ERIC) and multilocus sequence analysis (MLSA). Results There were 3 cases with CRKP HAI, with an incidence of 3.85% (3/78), which was statistically different from the incidence during the same period in 2022 and in May-June 2023 (P<0.05). Environmental hygienic monitoring revealed that CRKP was detected from the ventilator interface of bed 1, treatment table, and bedding of bed 9, with a detection rate of 4.84% (3/62). CRKP was not detected from 15 medical staff hand specimens and 3 NSICU air monitoring specimens. Three CRKP strains were detected through environmental hygiene monitoring, their antimicrobial resistance, resistance genes, and homology were consistent with those of CRKP strains detected from clinical specimens of patients. After taking a series of targeted measures, such as quarantine, strict cleaning and disinfection of the ward environment, strict implementation of disinfection and management of invasive devices, as well as strengthening the diagnosis and treatment in groups, disinfection of medical uniforms, and hand hygiene of medical staff, this event was effectively controlled. Conclusion This event can be classified as a suspected outbreak of CRKP HAI. It is speculated that inadequate disinfection management of invasive devices, incomplete disinfection of hospital environment, lack of grouping diagnosis and treatment of medical staff, and inadequate hand hygiene are the main causes for this suspected outbreak of HAI. Early identification of infection outbreaks, investigation of infection sources and transmission routes, and timely adoption of targeted measures are crucial to the control of infection outbreak.