Background and Aims: Timely and effective assessment scoring systems for predicting the mortality of patients with hepatitis E virus-related acute liver failure (HEV-ALF) are urgently needed. The present study aimed to establish an effective nomogram for predicting the mortality of HEV-ALF patients. Methods: The nomogram was based on a cross-sectional set of 404 HEV-ALF patients who were identified and enrolled from a cohort of 650 patients with liver failure. To compare the performance with that of the model for end-stage liver disease (MELD) scoring and CLIF-Consortium-acute-on-chronic liver failure score (CLIF-C-ACLFs) models, we assessed the predictive accuracy of the nomogram using the concordance index (C-index), and its discriminative abil-ity using time-dependent receiver operating characteristics (td-ROC) analysis, respectively. Results: Multivariate logis-tic regression analysis of the development set carried out to predict mortality revealed that γ-glutamyl transpeptidase, albumin, total bilirubin, urea nitrogen, creatinine, interna-tional normalized ratio, and neutrophil-to-lymphocyte ratio were independent factors, all of which were incorporated into the new nomogram to predict the mortality of HEV-ALF patients. The area under the curve of this nomogram for mortality prediction was 0.671 (95％ confidence inter-val: 0.602–0.740), which was higher than that of the MELD and CLIF-C-ACLFs models. Moreover, the td-ROC and deci-sion curves analysis showed that both discriminative ability and threshold probabilities of the nomogram were superior to those of the MELD and CLIF-C-ACLFs models. A similar trend was observed in the validation set. Conclusions: The novel nomogram is an accurate and efficient mortality pre-diction method for HEV-ALF patients.