PURPOSE: To explore the tumor response and propose a nomogram-based prognostic stratification for hepatocellular carcinoma (HCC) after drug-eluting beads transarterial chemoembolization (DEB-TACE). PATIENTS AND METHODS: From the database of two centers, patients who received DEB-TACE as an initial treatment were enrolled and divided into the training and validation sets. The tumor response after DEB-TACE was estimated according to the Modified Response Evaluation Criteria in Solid Tumors. Using the independent survival predictors in the training set, a nomogram was constructed and validated internally and externally by measuring concordance index (C-index) and calibration. A prognostic stratification based on the nomogram was established. RESULTS: A total of 335 patients met the inclusion criteria for the study. Alkaline phosphatase level, tumor maximum diameter, tumor capsule and portal vein invasion were interrelated with the achievement of complete release after DEB-TACE. Alpha-fetoprotein level, Child-Pugh class, tumor maximum diameter, tumor number, tumor extent and portal vein invasion were integrated into the nomogram. The nomogram demonstrated good calibration and discrimination, with C-indexes of 0.735 and 0.854 and higher area under the curve (AUC) than BCLC and CNLC staging systems in the internal and external validation sets. The prognostic stratification classified patients into three different risk groups, which had significant differences in survival, complete release and objective response rate between any two groups ( < 0.05). CONCLUSION: The nomogram-based prognostic stratification has a good distinction and may help to identify the patients benefiting from DEB-TACE.