Objective To investigate the clinical effect of plasma perfusion (PP) combined with plasma exchange (PE) in the treatment of acute-on-chronic liver failure (ACLF) .Methods A total of 72 patients with ACLF who were admitted to The Second People's Hospital of Lanzhou from January 2014 to December 2015 were enrolled.In addition to internal medication, all the patients were treated with the artificial liver support system (once every 3-4 days based on the patients' conditions, 1-3 times on average for each patient) .According to the difference in therapies, the patients were divided into combination group with 40 patients (PP combined with PE and a total of 107 case times) and control group with 32 patients (PE alone and a total of 85 case times) .Total bilirubin (TBil) , alanine aminotransferase (ALT) , and prothrombin time were recorded before treatment, after surgery, and at 72 hours after surgery.Clinical outcome was evaluated after 4 weeks of treatment.The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups.Results The overall response rate of all patients was 63.89% (46/72) .At 72 hours after surgery, there was a significant difference in the level of ALT between the combination group and the control group (319.54 ± 86.23 U/L vs354.75 ± 100.76 U/L, t=2.60, P<0.05) .Both groups had significant reductions in TBil and ALT after surgery (combination group: t =6.69 and 15.84, P<0.05; control group: t=5.34 and 14.38, P<0.05) and at 72 hours after surgery (combination group: t=3.24 and8.83, P<0.05; control group: t=2.40 and 4.61, P<0.05) .Both groups had significant changes in prothrombin time activity after surgery (t=4.83 and 5.01, both P<0.05) .There were no significant differences in the incidence rates of pruritus and rash between the two groups, while there was a significant difference in the incidence rate of perioral or limb numbness between the two groups (10.28% vs31.76%, χ2=9.11, P<0.05) .Conclusion Both PE combined with PP and PE alone can effectively improve the clinical outcome of ACLF patients with similar response rates; however, PE combined with PP can save the amount of plasma by 40%-50% and reduce the incidence of the adverse effects of PE and has higher safety.Meanwhile, it is in accordance with the social reality of a shortage of blood resources.Therefore, it is a better choice in clinical treatment.