Objective：This article aims to investigate the efficiency of a model combined serum lactate dehydrogenase（LDH）level and model for end-stage liver disease（MELD）MELD-LDH on evaluating the prognosis of patients with acute-on-chronic liver failure（ACLF），and to study the correlation between serum LDH and different levels of multiple system damage in order to improve the awareness and treatment of ACLF. Methods：This study used a retrospective method to collect clinical data of 119 patients with ACLF admitted to the First Affiliated Hospital of Nanjing Medical University from October 2015 to August 2019. According to the prognosis of 28 days after admission，they were divided into the survival group（n=90）and the death group（n=29）. Univariate and multivariate regression analysis methods were used to analyze the relevant factors affecting the prognosis of patients with ACLF. MELD-LDH model was established to verify its efficacy and explore the correlation between serum LDH and the levels of multiple organ damage. Results：The results showed that serum LDH levels were independent risk factors affecting the prognosis of patients with ACLF（OR=1.015，P=0.002）. LDH was significantly higher in patients with renal failure and hepatic encephalopathy（P=0.002，P=0.018）. MELD-LDH model was significantly better than MELD scores in predicting 28-day and 90-day clinical outcomes（P=0.028，P=0.002）. Conclusion：High serum LDH level is an independent risk factor for 28-day mortality in patients with ACLF，and it is closely related to renal failure and hepatic encephalopathy. MELD-LDH model established by combining LDH and MELD scores has a better predictive effect on the 28-day and 90-day prognosis of patients with ACLF.