BACKGROUND: Accurate prediction of tumor response after drug-eluting beads transarterial chemoembolization (DEB-TACE) remains challenging in hepatocellular carcinoma (HCC), given tumor heterogeneity and dynamic changes over time. Existing prediction models based on single timepoint imaging do not capture dynamic treatment-induced changes. This study aims to develop and validate a predictive model that integrates deep learning and machine learning algorithms on longitudinal contrast-enhanced MRI (CE-MRI) to predict treatment response in HCC patients undergoing DEB-TACE. METHODS: This retrospective study included 202 HCC patients treated with DEB-TACE from 2004 to 2023, divided into a training cohort ( = 141) and validation cohort ( = 61). Radiomics and deep learning features were extracted from standardized longitudinal CE-MRI to capture dynamic tumor changes. Feature selection involved correlation analysis, minimum redundancy maximum relevance, and least absolute shrinkage and selection operator regression. The patients were categorized into two groups: the objective response group ( = 123, 60.9%; complete response = 35, 28.5%; partial response = 88, 71.5%) and the non-response group ( = 79, 39.1%; stable disease = 62, 78.5%; progressive disease = 17, 21.5%). Predictive models were constructed using radiomics, deep learning, and integrated features. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the models. RESULTS: We retrospectively evaluated 202 patients (62.67 ± 9.25 years old) with HCC treated after DEB-TACE. A total of 7,182 radiomics features and 4,096 deep learning features were extracted from the longitudinal CE-MRI images. The integrated model was developed using 13 quantitative radiomics features and 4 deep learning features and demonstrated acceptable and robust performance with an receiver operating characteristic curve (AUC) of 0.941 (95%CI: 0.893–0.989) in the training cohort, and AUC of 0.925 (95%CI: 0.850–0.998) with accuracy of 86.9%, sensitivity of 83.7%, as well as specificity of 94.4% in the validation set. CONCLUSIONS: This study presents a predictive model based on longitudinal CE-MRI data to estimate tumor response to DEB-TACE in HCC patients. By capturing tumor dynamics and integrating radiomics features with deep learning features, the model has the potential to guide individualized treatment strategies and inform clinical decision-making regarding patient management. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40644-025-00926-5.