Objective:To observe the clinical efficacy of Lishi Jiedu Formula (LSJD) for oral administration and Tongfu Zhuyu Formula (TFZY) for enema combined with conventional therapy in treating hepatitis B virus (HBV) associated acute-on-chronic liver failure (HBV-ACLF). Methods139 patients with HBV-ACLF were randomly assigned into treatment group (72 patients) and control group (67 patients). The control group was treated with comprehensive medical treatment, while the treatment group was treated with LSJD and TFZY on the basis of the treatment measures of the control group. The two groups were treated for 8 weeks. Survival rate was observed, and liver function [alanine aminotransferase (ALT), total bilirubin (TBil) and cholinesterase (CHE)], prothrombin activity (PTA), hepatitis B virus-DNA (HBV-DNA), and score of model for end-stage liver disease (MELD) were compared at 2,4 and 8 weeks of treatment and 12 weeks after treatment.  Results:①The total survival rate and the 2- and 4-week survival rates were 65.3%, 86.1% and 95.2% respectively in the treatment group, and 43.3%, 67.2% and 80.0% respectively in the control group, with significant difference between the two groups (P<0.05). ②There were significant differences in the levels of serum ALT, TBil, CHE and PTA and MELD scores in the groups at 2,4 and 8 weeks of treatment and at 12 weeks after treatment compared to those before treatment (P<0.05); there were significant differences in the levels of serum ALT, TBil, CHE and PTA and MELD scores between the two groups at 4 and 8 weeks of treatment (P<0.05). ③The level of HBV-DNA decreased in both groups at 2,4 and 8 weeks of treatment and at 12 weeks after treatment compared to that before treatment (P<0.05); the level was lower in the treatment group than in the control group at 8 weeks of treatment (P<0.05).  Conclusion:LSJD for oral administration and TFZY for enema combined with conventional therapy shows satisfactory effect in treating HBV-ACLF. Compared with conventional therapy, it improves the liver function and coagulation function, reduces the level of HBV-DNA, and improves the short-term survival rate of patients with HBV-ACLF.