This study aimed to evaluate the efficacy and safety of entecavir, lamivudine and telbivudine for treating patients with HBV-ACLF and to validate the Tongji prognostic predictor model (TPPM) in these patients. In this retrospective study, we enrolled 283 patients with HBV-ACLF (100 treated with entecavir, 98 treated with lamivudine and 85 treated with telbivudine). There were no significant differences in baseline clinical and virological characteristics among patients treated with entecavir, telbivudine or lamivudine. There were no significant differences in the 4- and 12-week survival rates of entecavir-, telbivudine- and lamivudine-treated patients (79.00, 81.18 and 86.73 %, respectively, at 4 weeks; 67.00, 65.88 and 73.47 %, respectively, at 12 weeks). Patients in all three groups achieved an improvement in the model for end-stage liver disease (MELD) score. Using the Hosmer-Lemeshow test, the validation of the TPPM score for HBV-ACLF demonstrated a good degree of fit with disease prognosis. Based on this unique group of patients, the TPPM score with an AUC of 0.787 was superior to the MELD score, which had an AUC of 0.736 in the prediction of 12-week mortality. The TPPM had an AUC of 0.733, and the MELD score had an AUC of 0.672 in the prediction of 4-week mortality. Using a cutoff value of 0.22 for 12-week mortality prediction by the TPPM, the positive predictive value was 49.66 %, with a negative predictive value of 89.55 %. Treatment with nucleoside analogs including entecavir, lamivudine and telbivudine prevented disease progression and increased the survival of patients with HBV-ACLF. Validation of the established TPPM scoring system in this study confirmed its superior predictive value for HBV-ACLF patients when compared with the MELD system.