Objective This study aimed to assess the diagnostic utility of systemic immune-inflammation index (SII) for catheter-related bloodstream infection (CRBSI) among patients undergoing maintenance hemodialysis (MHD).  Methods  A retrospective analysis was conducted on the clinical data of 196 MHD patients. Participants were categorized into a tunneled central catheter (TCC) group (n=90) and a non-tunneled central catheter (NCC) group (n=106). Each group was subdivided into an infection subgroup and a control subgroup. SII was calculated from the collected clinical parameters. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic performance of SII for CRBSI. Changes of SII level before and after anti-infective treatment in infected patients were analyzed. In addition, differences in inflammatory markers between Gram-positive (G+) and Gram-negative (G-) bacterial infections were compared. The discriminative ability of SII, C-reactive protein (CRP), and other biomarkers for pathogen type was also assessed.  Results  The 90 patients in TCC group included 28 in infection subgroup and 62 in control subgroup; the 106 patients in NCC group were comprised of 27 in infection subgroup and 79 in control subgroup. SII level was significantly higher in the infection subgroups than in the control subgroups, including comparison of the subgroups in TCC group (Z=-5.429, P<0.001) and that of the subgroup in NCC group (Z=-5.850, P<0.001). Anti-infection therapy achieved a significant reduction of SII among infection patients (t=6.173, P<0.001). ROC analysis indicated that the area under the curve (AUC)  of SII for the diagnosis of CRBSI was 0.859 with the sensitivity of 82.2% and the specificity of 78.5% in TCC group, while the AUC of SII for the diagnosis of CRBSI was 0.878 with the sensitivity of 85.1% and the specificity of 77.2% in NCC group. CRP level was significantly higher in patients with G- infections than in those with G+ bacterial infections (Z=-4.236, P<0.001). For discriminating between G+ and G- infections, the AUC of CRP (AUC=0.875) was higher than the AUCs of neutrophils (AUC=0.699, Z=6.442, P<0.01), lymphocytes (AUC=0.671, Z=4.531, P<0.001), and SII (AUC=0.553, Z=3.818, P<0.001).  Conclusion  SII and C-reactive protein are important clinical indicators for the early diagnosis of CRBSI.