OBJECTIVE: The study aimed to develop and externally validate multiparametric MRI (mpMRI) radiomics-based interpretable machine learning (ML) model for preoperative differentiating between benign and malignant prostate masses. METHODS: Patients who underwent mpMRI with suspected malignant prostate masses were retrospectively recruited from two independent hospitals between May 2016 and May 2023. The prostate mass regions in T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) MRI images were segmented by ITK-SNAP. PyRadiomics was utilized to extract radiomic features. Inter- and intraobserver correlation analysis, t-test, Spearman correlation analysis, and the least absolute shrinkage and selection operator (LASSO) algorithm with a five-fold cross-validation were applied for feature selection. Five ML learning models were built using the chosen features. Model performance was evaluated with internal and external validation, using area under the curve (AUC), calibration curves, and decision curve analysis to select the optimal model. The interpretability of the most robust model was conducted via SHapley Additive exPlanation (SHAP). RESULTS: A total of 567 patients were enrolled, consisting of the training (n = 352), internal test (n = 152), and external test (n = 63) sets. In total, 2,632 radiomic features were extracted from regions of interest (ROIs) of T2WI and DWI images, which were reduced to 18 via LASSO. Five ML models were established, among which the random forest (RF) model presented the best predictive ability, with AUCs of 0.929 (95% confidential interval [CI]: 0.885-0.963) and 0.852 (95% CI: 0.758-0.934) in the internal and external test sets, respectively. The calibration and decision curve analyses confirmed the excellent clinical usefulness of the RF model. Besides, the contributing relations of the radiomic features were uncovered using SHAP. CONCLUSIONS: Radiomic features from mpMRI combined with machine learning facilitate accurate preoperative evaluation of the malignancy in prostate masses. SHAP can disclose the underlying prediction process of the ML model, which may promote its clinical applications.