Abstract: Objective To investigate the effect of artificial liver support system (ALSS) on the treatment of hepatitis E virus infection complicated by hyperbilirubinemia.Methods A total of 52 patients with hepatitis E virus infection complicated by hyperbilirubinemia were treated with artificial liver support system on the basis of conventional therapy.43 patients were included in the study as a control.Clinical parameters including serum TBIL, AST, ALT, BUN, ALB, PTA and Cr were measured.Results The clinical symptoms of hepatitis E patients complicated by hyperbilirubinemia were improved among the treatment group.The serum levels of TBIL, ATL, AST, TBA, ALB and PTA increased significantly (P<0.05) .No statistical significance was observed in the levels of BUN and Cr.The treatment responses were 84.62% and 55.81% in the treatment group and in the control group, respectively (P<0.05) .The level of serum TBIL increased only in seven patients.Conclusion The ALSS is effective in treating hepatitis E virus infection complicated by hyperbilirubinemia on the basis of conventional therapy.The increase in the serum level of TBIL can used to monitor the prognosis of hepatitis E virus infection complicated by hyperbilirubinemia after ALSS treatment.