Abstract: Objective To investigate the factors affecting the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF),and establish a new prognosis model. Methods Totally 266 patients with HBV-ACLF who were hospitalized in the Affiliated Hospital of Southwest Medical University from March 2014 to March 2018 were enrolled in our study and divided into survival group and death group according to their prognosis at 90 days.The results of routine hematological tests,liver function,renal function,coagulation test,complications and other indicators at admission were analyzed.Univariate analysis and multivariate logistic regression analysis were used to analyze the risk factors for death of the patients,and then a new prediction model was established.Area under the receiver operating characteristic (ROC) curve was used to evaluate the prognostic value of end-stage liver disease (MELD) and the new model. Results Of the 266 HBV-related ACLF patients,84 patients died and the mortality rate was 31.6%.RDW (OR:1.135,95% CI:1.046-1.231),hepatic encephalopathy (HE) (OR:3.625;95% CI:1.744-7.535),creatinine (Cr)(OR:1.016;95% CI:1.007-1.025) and INR (OR:1.999;95% CI:1.415-2.825) were the independent prognostic factors for predicting the prognosis of HBV-ACLF patients (all P<0.05).Area under the ROC curve (AUC) of the new model was significantly higher than that of the MELD (0.824 vs 0.779,P=0.027). Conclusion RDW,HE,Cr and INR are the independent risk factors predicting the 90-day prognosis of patients with HBV-ACLF.The new model based on the four indices has better predicting value than MELD.