Objective To explore the influencing factors of long-term hemodialysis catheter-associated bloodstream infection, and evaluate serum human neutrophil lipocalin (HNL), interleukin-6 (IL-6), procalcitonin (PCT). The predictive value of PCT for long-term hemodialysis catheter-related bloodstream infection (CRBSI). Method A total of 82 patients with long-term hemodialysis in Suqian Hospital of Jiangsu Provincial People's Hospital from August 2022 to February 2024 were selected as the study subjects and divided into two groups, namely CRBSI group (n=21) and non-CRBSI group (n=61), according to the CRBSI standard in the Expert Consensus on Vascular Access for Hemodialysis in China. The distribution of pathogenic bacteria, baseline data, disease data, dialysis status and serum HNL, IL-6 and PCT levels in the CRBSI group were analyzed by univariate and multivariate Logistic regression analysis, and the expression levels of serum HNL, IL-6 and PCT in the two groups were compared. Receiver operating characteristic (ROC) was plotted, and the diagnostic efficacy of HNL, IL-6 and PCT for CRBSI was analyzed by using the area under the curve (AUC). Result Blood culture of 21 patients in CRBSI group was performed to identify 48 isolates of pathogenic bacteria. Among them, 10 strains (20.83%) are infected by Gram-negative bacteria (G-) and 38 strains (79.17%) are infected by Gram-positive bacteria (G+). The occurrence of CRBSI was the dependent variable of Logistic regression analysis. Whether CRBSI occurred was the dependent variable of Logistic regression analysis. Logistic regression analysis showed that femoral vein placement site, dialysis time ≥1 year, catheter type without tunnel catheter, increased HNL, IL-6 and PCT were risk factors(P<0.05). The expression levels of serum HNL, IL-6 and PCT in CRBSI group were higher than those in non-CRBSI group (t=3.795, 6.450 and 3.670, all P<0.05). The AUC of HNL, IL-6, PCT and the combined diagnosis of CRBSI were 0.724, 0.875, 0.735 and 0.917, respectively, and the area under the combined curve of the three was the largest. The sensitivity and specificity of the combined prediction of CRBSI were 95.24% and 85.25%, respectively. The sensitivity was significantly higher than that of HNL, IL-6 and PCT single index, and the specificity was significantly higher than that of IL-6 and PCT single index, which had high predictive value (P<0.05). There was no significant difference between the specificity and HNL (P>0.05). Conclusion Elevated serum HNL, IL-6, and PCT have significant value in predicting the risk of long-term CRBSI in hemodialysis. Therefore, the combined application of HNL, IL-6 and PCT in the clinic is conducive to early identification of the risk of CRBSI, providing a strong basis for clinical treatment and prognosis assessment, so as to reduce the risk of infection and case fatality rate of hemodialysis patients.