Objective To determine whether plasma exchange combined with hemofiltration influences the peripheral blood levels of interleukin (IL) -17 and/or IL-6 in patients with hepatitis B virus (HBV) -related acute-on-chronic liver failure (ACLF) and investigate its clinical significance.Methods Thirty patients diagnosed with HBV-related ACLF received a single treatment of plasma exchange combined with hemofiltration.This group was subdivided according to 72 h outcomes of improvement (n = 19) or deterioration (n = 11) .Control groups were composed of chronic hepatitis B patients (CHB;n = 19) and healthy individuals (HC;n = 20) .Blood samples were collected from all study participants to measure concentrations of IL-17 and IL-6 by enzyme-linked immunosorbent assay and biochemical parameters with an automatic analyzer.Intergroup differences were statistically analyzed for significance.Results IL-17 and IL-6 were markedly up-regulated in the HBV-related ACLF group compared with the CHB and HC groups.The plasma exchange combined with hemofiltration treatment significantly reduced the serum concentrations of IL-17 and IL-6 (vs.pre-treatment levels: t = 35.1, P < 0.001 and t = 33.4, P < 0.001, respectively) .In addition, the indexes of extracorporeal removal of IL-17 and IL-6 were higher in the improved subgroup than in the deterioration subgroup (t = 3.8, P < 0.05 and t = 3.9, P < 0.05, respectively) and were negatively associated with the MELD score of the HBV-related ACLF patients in both subgroups (r = 0.53, P < 0.05 and r = 0.43, P < 0.05, respectively) .Conclusion The enhanced serum concentrations of IL-17 and IL-6 in HBV-related ACLF patients were markedly reduced by a single treatment of plasma exchange combined with hemofiltration.The removal efficiency of plasma exchange combined with hemofiltration for serum IL-17 and IL-6 may be a short-term prognostic indicator of HBV-related ACLF patients, possibly due to the reduced risk of inflammation-related damage mediated by these two cytokines.