Objective To explore the independent risk factors for central line-associated bloodstream infection (CLABSI), provide basis for developing intervention measures for infection prevention and control as well as conducting targeted treatment. Methods Patients who were diagnosed with CLABSI in a hospital from January 2019 to December 2023 were recruited retrospectively and defined as the infection group. According to 1 ∶4 propensity score matching method, patients who received central venous catheter (CVC) without infection were taken as the control group. With whether CLABSI occurred as the dependent variable, the possible risk factors of the matched two groups as the independent variables, logistic regression analysis was conducted, and independent risk factors for patients developing CLABSI were explored. Results A total of 42 patients in the CLABSI group and 168 patients in the non-CLABSI group were matched. Multivariate logistic regression analysis showed that high score of acute physiology and chronic health evaluation (APACHE) Ⅱ (OR=1.217, 95%CI ［1.094-1.357］, P<0.001), long duration of central venous catheterization (OR=1.273, 95%CI ［1.157-1.400］, P<0.001), and femoral venous catheterization (OR=6.846, 95%CI ［1.511-31.014］, P=0.013) were independent risk factors for CLABSI. A total of 118 strains of pathogens were isolated from 42 CLABSI patients, with Gram-negative bacteria being the majority (n=56). Conclusion High score of APACHE Ⅱ, long duration of central venous catheterization, and femoral venous catheterization are independent risk factors for CLABSI. The main pathogens are Gram-negative bacilli. Strict prevention and control measures for CLABSI should be implemented to reduce the risk of infection.