Acute-on-chronic liver failure (ACLF) has been a hot spot in the field of liver disease research in recent years, with high morbidity, rapid course change and high mortality. Currently, there is the absence of specific treatment in clinical practice. Liver transplantation has the best therapeutic effect, but it is prone to have internal environment disorder and liver cell death after transplantation, which leads to the failure of transplantation.In recent years, with the development of molecular biology, scholars have explored the treatment of ACLF at the molecular level, and more and more molecular signaling pathways related to the treatment of ACLF have been discovered. Modulating the relevant signaling pathways to reduce the mortality of liver cells after transplantation may effectively improve the success rate of transplantation. In this review, we introduce some signaling pathways related to cell death and their research progress in acute-on-chronic liver failure.