Objective To construct a hybrid bioartificial liver support system and to investigate its safety and efficacy in patients with hepatitis B virus ( HBV) - related acute- on- chronic liver failure ( ACLF) . Methods A hollow fiber bioreactor was constructed using cultured HepG2 cells transfected with human augmenter of liver regeneration gene. Patients with HBV- related ACLF who were hospitalized in our hospital from May2009 to August 2011 were randomly divided into treatment group ( n = 10) and control group ( n = 10) . The treatment group was treated using the hybrid bioartificial liver support system, while the control group was treated with conventional plasma exchange. Comparison of means between the two groups was made by independent- samples t test, and comparison of variables before and after treatment was made by paired t test. Results Of the 10 patients in treatment group, 7 had improvement in clinical symptoms and were discharged, 1 died of hepatic encephalopathy, 1 died of hepatorenal syndrome, and 1 died of liver failure after discharge. Of the 10 patients in control group, 5 survived, 1 underwent liver transplantation, and 4 died of liver failure. Before treatment, the treatment group and control group had model for end- stage liver disease ( MELD) scores of 24. 26± 2. 54 and 24. 71 ± 2. 79, respectively, without significant difference between the two groups ( t = 1. 971, P = 0. 064) . The treatment group had MELD scores of 21. 71 ± 2. 92, 22. 10 ± 4. 46, and 19. 90 ± 5. 43 after 3 days, 1 week, and 4 weeks, respectively, of treatment. At the end of one-year follow- up, the mean serum alpha- fetoprotein levels were 14. 24 ng / ml in treatment group and 11. 32 ng / ml in control group, and no space- occupying lesions in the liver were found through abdominal ultrasound. Conclusion The constructed hybrid bioartificial liver support system is effective and safe in the treatment of HBV- related ACLF.