Background: The gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is a new noninvasive marker for assessing liver fibrosis. We aimed to evaluate the performance of GPR for prediction of 90-day mortality in patients with acute-on-chronic liver failure (ACLF). Methods: A total of 355 patients with HBV-associated ACLF were enrolled from two clinical centers and divided into training group (n = 210) and validation group (n = 145). Potential risk factors for 90-day mortality were analyzed. Results: Age, MELD score and GPR were independent risk factors associated with ACLF prognosis. A new scoring system (MELD-GPR) was developed. MELD-GPR = 9.211 - 0.029 x age - 0.290 x MELD - 0.460 x GPR. For ACLF patients with liver cirrhosis, the area under the receiver operating characteristic curve (AUROC) of MELD-GPR was 0.788, which was significantly higher than that of MELD and MELD-Na (0.706 and 0.666, respectively). Patients were stratified into three groups according to MELD-GPR scores (high risk: < -0.19, intermediate risk: - 0.19-0.95, and low risk: > 0.95), and the high-risk group (MELD-GPR < -0.19) had a poor prognosis (P < 0.01). For ACLF patients without liver cirrhosis, MELD-GPR < 0.95 predicted a poor prognosis. Conclusions: Incorporating GPR into MELD may provide more accurate survival prediction in patients with HBV-ACLF.