Abstract Background and Aims Interleukin-6 (IL-6) is a key mediators of inflammation and has been linked to the severity and mortality of COVID-19-Omicron in the general population. With higher mortality rates observed in maintenance hemodialysis (MHD) patients infected with COVID-19-Omicron, the study aimed to examine the correlation between IL-6 levels and mortality in this patient population and to indentify the optimal IL-6 level for predicting the risk of death. Method The retrospective observational study was conducted in MHD patients diagnosed with COVID-19-Omicron infection between December 01, 2022 and January 31, 2023 at the Third Affiliated Hospital of Southern Medical University during the first wave of infection in COVID-19-Omicron outbreak in China. Clinical and biochemical data were collected during the infection, IL-6 levels of the patients were measured before consecutive dialysis sessions by a commercial kit. The Cox model was used to investigate the risk factors of mortality, meanwhile, ROC curve to determine the cut off value of IL-6 levels on mortality. Results A total of 162 MHD patients infected with COVID-19-Omicron were included in this study. During a median follow-up period of 40 days, 10 (6.2%) deaths occurred due to COVID-19 infection. IL-6 levels were significantly higher in patients who died. Univariate Cox regression analyses showed that the risk factors associated with death included IL-6 levels (HR: 1.009; p<0.001), C-reactive protein (HR: 1.01; p = 0.016), serum potassium (HR: 2.258; p = 0.015, procalcitonin(PCT) (HR: 1.01; p = 0.048), and the Charlson comornidity index(CCI)(HR: 1.34; p = 0.002). However, in multivariate analysis, only IL-6 levels was independently associated with all-cause mortality(HR: 1.01; p = 0.001).The ROC curve and Kaplan-Meier survival analysis revealed a significantly worse survival risk among MHD patients with higher serum IL-6 levels (≥104.87 pg/mL) (sensitivity:100%; specificity:78.2%; AUC: 0.92; p = 0.001). Conclusion Serum IL-6 levels greater than 104.87 pg/mL were associated with an increased risk of all-cause mortality in MHD patients infected with COVID-19-Omicron. Hemoperfusion or hemofiltration to remove IL-6 may provide appropriate treatment options for hemodialysis patients with COVID-19-Omicron.