Abstract: There are many hot and difficult points in the diagnosis and treatment of liver failure, and controversies still exist both at home and abroad. In the Western countries, the diagnosis of acute liver failure (ALF) does not depend on history of chronic liver disease. In Asian-Pacific region, including China, it is believed that the basis of chronic liver disease is an important factor determining disease characteristics. Etiological treatment is believed to be very important in the treatment of ALF. It has been confirmed that the application of NAC can significantly improve the overall survival rate of ALF induced by drug-induced liver injury. However, some scholars believe that the use of long-course NAC can not increase patients' benefits, which still needs further confirmation. For indications of HBV-ALF antiviral therapy, HBV DNA is not required to be positive in any guidelines except the guidelines in China. Although patients with HCV-related cirrhosis can achieve high SVR rate with DAA antiviral therapy, the clinical safety profile of various DAA treatments should be fully evaluated. Prophylactic use of antibiotics may be beneficial in patients with liver failure, but there is also an argument for lacking of evidence. Empirical antimicrobial therapy should be formulated according to the specific situation and non-antibiotic treatment can be tried to prevent infection including probiotics, gastrointestinal motility regulators, simvastatin, etc. It has been found that immunomodulators play an important role in the treatment of liver failure, but the timing, indications, dosage, course of treatment, specificity and adaptability of different liver injuries remain further clinical research. In conclusion, clinical experts should apply guidelines and consensus flexibly and rationally, and conduct in depth research based on specific situations as well as the guidelines and consensus, so as to improve the level of diagnosis and treatment of liver failure.