Objective To explore the risk factors for bloodstream infection related to non-cuffed catheter (NCC) of hemodialysis, and provide basis for the prevention and control of catheter-related bloodstream infection (CRBSI) in hemodialysis patients. Methods A total of 127 hospitalized patients who underwent NCC hemodialysis and developed CRBSI in the department of nephrology of a hospital from January 2015 to December 2024 were selected as the case group. According to a matching ratio of 1∶2, and with gender, renal failure type, and NCC catheterization time ±30 days as matching conditions, 254 hospitalized patients who underwent NCC hemodialysis but did not develop CRBSI were selected as the control group. Data on general information, underlying diseases, nutritional status, treatment methods of two groups of patients were collected. Univariate and multivariate conditional logistic regression analyses were conducted using SAS 9.4 software. Results Among 381 patients, 261 (68.50%) were male and 120 (31.50%) were female. Gram-positive bacteria were the main pathogens of NCC-related CRBSI. Patients’ body mass index (BMI), education level, combined cardiovascular disease, combined diabetes, treatment history of end-stage renal disease, length of hospital stay before catheterization, and blood transfusion therapy during hemodialysis period were potential risk factors for CRBSI in NCC hemodialysis patients. Multivariate conditional logistic analysis showed that patients’ high BMI (OR=1.103, 95% CI: 1.036-1.175), combined cardiovascular disease (OR=1.810, 95% CI: 1.073-3.054), previous treatment history for end-stage renal disease (OR=1.737, 95% CI: 1.047-2.884), length of hospital stay before catheterization (OR=1.065, 95% CI: 1.018-1.113), and blood transfusion during hemodialysis (OR=2.866, 95% CI: 1.611-5.100) all increased the risk of developing CRBSI in NCC hemodialysis patients. Conclusion Controlling patients’ weight, strengthening screening of high-risk patients, selecting appropriate timing for hemodialysis, and standardizing hemodialysis techniques can effectively reduce the risk of CRBSI in NCC hemodialysis patients.