Objective To compare the differences in epidemiological characteristics, pathogen distribution, and prognosis of central line-associated bloodstream infection (CLABSI) between children in intensive care units (ICUs) and in non-ICUs, identify key influencing factors, and provide basis for developing individualized prevention and control strategies. Methods 391 children with CLABSI in a tertiary children’s hospital in Guangzhou City between January 1, 2022 and June 30, 2025 were retrospectively enrolled in the analysis. Children were divided into an ICU group (n=134) and a non-ICU group (n=257) based on their hospitalization wards. Basic information, catheter-related information, infection-related information, and prognostic indicators of children were collected. SPSS 26.0 was adopted to conduct statistical analysis, categorical data were analyzed by χ² test and quantitative data were compared using non-parametric test. After univariate analysis of factors influencing the risk of 30-day all-cause mortality was performed using χ² test and non-parametric test, factors with P≤0.05 were included in a multivariate logistic regression model for further analysis. Results During the study period, the incidence of CLABSI in ICUs (1.06%-1.53%) remained stable with minor fluctuations, while that in the hematology-oncology ward (1.54‰-2.58‰) increased and was higher than that in ICUs; the incidence in other general wards was 1.45‰. Pathogens in ICUs and hematology-oncology ward were mainly Gram-negative bacteria (accounting for 48.96% and 57.56%, respectively), whereas Gram-positive bacteria were the main pathogens in other general wards (66.67%). The overall mortality of children was 5.37%(21/391), with mortality of 10.45% (14/134) in ICUs and 3.76% (7/186) in the hematology-oncology ward. Multivariate analysis revealed that the longer the hospitalization stay after infection, the lower the risk of all-cause mortality within 30 days (OR=0.884, 95%CI: 0.812-0.963). Anemia (OR=6.357, 95%CI: 1.246-32.429) and pneumonia (OR=5.264, 95%CI: 1.035-26.766) were independent risk factors for mortality in children in hematology-oncology ward. Conclusion The incidence of CLABSI is high in children from the hematology-oncology ward, with common pathogen spectra across different wards. Skin-derived bacteria (e.g. Staphylococcus epidermidis) account for a relatively high proportion in other general wards. Infection control measures targeting specific pathogens should be strengthened, with particular attention to children with anemia and pneumonia in the hematology-oncology ward.