ABSTRACT This study aimed to develop a prediction model for the prognosis of patients with Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). 122 patients were divided into survival group and death group according to 90-day prognosis after diagnosis. Risk factors affecting the prognosis were identified by the logistic regression analysis and then were used to establish an FT3-related prediction model. Age, proportion of liver cirrhosis, AST, TBil, INR, Cr, Na, WBC, and several scores (CTP, MELD, MELD-Na, CLIF-SOFA, CLIF-OF, and AARC scores) of the death group were significantly higher than that of the survival group on admission. FT3 and Na were protective factors for the prognosis of patients; Age, TBil, INR, HE grading, and Cr were risk factors. FT3 levels were (2.79 ± 0.34) (95%CI 2.73–2.87) pmol/L for the survival group and (2.20 ± 0.20) (95%CI 2.11–2.29) pmol/L for the death group. The level of FT3 in survival group was significantly higher than that of the death group in patients regardless of gender, initial liver disease, and liver failure stages (P < 0.05). The ROC curve for FT3-related prognostic model score was 0.923 (95%CI 0.809–0.947), significantly higher than that of the CTP, MELD, MELD-Na, CLIF-SOFA, CLIF-C OF, and AARC scores (P < 0.001). The FT3-related prediction model has good predictive value for 90-day prognosis.