Abstract: OBJECTIVE To investigate the causes of the abnormal increase in the detection rate of Staphylococcus aureus (SA) and methicillin-resistant S. aureus (MRSA) among hemodialysis patients in the nephrology department of a tertiary hospital, and to trace the source of infection and evaluate the prevention and control effect. METHODS An epidemiological investigation was conducted on 4 patients with central line-associated bloodstream infections in the nephrology department of a tertiary hospital from Sep. 2025 to Oct. 2025. Environmental specimens and specimens from medical staff were collected for bacterial culture and antimicrobial susceptibility testing. Comprehensive prevention and control measures were implemented. The Poisson exact test was employed to compare the incidence rate ratio (IRR) and analyze the infection risk. RESULTS A total of four CLABSI were confirmed, including two MRSA and two SA cases. The CLABSI incidence rate in Oct. (7.77‰) exhibited a significant increase. The Poisson exact test showed that the infection risk in Oct. was 10.69 times higher than in other months (IRR=10.69, 95% CI: 1.80-64.08, P=0.031). No SA was detected in the specimens from environmental surfaces or medical staff's hands, whereas four out of six dialysis operators carried SA in their nasal cavities, including one MRSA strain with an antimicrobial susceptibility profile identical to that of the patient isolates (resistant to oxacillin, penicillin and clindamycin). After comprehensive interventions, no CLABSI cases were reported in the ward from Nov. to Dec., and all four nasal carriers tested negative following mupirocin decolonization. CONCLUSIONS This cluster of SA/MRSA infections is highly associated with nasal colonization among medical staff, with the transmission chain of "colonization→hand contamination→catheter manipulation→patient infection." Although molecular homology testing is not performed, sufficient lines of epidemiological evidence can prove that comprehensive prevention measures effectively halt transmission.