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Background: Alpha-fetoprotein (AFP) has been shown to predict the prognosis of liver disease in several studies. This study aimed to evaluate the prognostic value of stratified AFP in patients with acute-on-chronic hepatitis B liver failure (ACHBLF)., Methods: A total of 192 patients were included and AFP were categorized into quartiles. The prognostic value was determined for overall survival (OS) and assessed by Kaplan-Meier analysis. Univariate and multivariate Cox proportional hazard regression analyses studied the association of all independent parameters with disease prognosis., Results: The optimal cut-off points of AFP were: (Q1) 252.3-4800.0 ng/ml, (Q2) 76.0-252.2 ng/ml, (Q3) 18.6-75.9 ng/ml, and (Q4) 0.7-18.5 ng/ml. Based on the Kaplan-Meier analysis of the OS, each AFP quartile revealed a progressively worse OS and apparent separation (log-rank P = 0.006). The second-highest quartiles of AFP (Q2) always demonstrated an extremely favorable short-term survival. Combining the lowest AFP quartiles with a serum sodium < 131mmol/L or an INR ≥ 3.3 showed a poor outcome (90-days survival of 25.0% and 11.9% respectively)., Conclusions: Stratified AFP could strengthen the predictive power for short-term survival of patients with ACHBLF. Combining AFP quartiles with low serum sodium and high INR may better predict poor outcome in ACHBLF patients.