PurposePreoperative identification of hippocampal sclerosis (HS) is crucial to successful surgery for mesial temporal lobe epilepsy (MTLE). We aimed to investigate the diagnostic performance of hippocampal radiomics models based on T2 fluid-attenuated inversion recovery (FLAIR) images in MTLE with HS. MethodsWe analysed 210 cases, including 172 HS pathology-confirmed cases (100 magnetic resonance imaging [MRI]-positive cases [MRI + HS], 72 MRI-negative HS cases [MRI − HS]), and 38 healthy controls (HC). The hippocampus was delineated slice by slice on an oblique coronal plane by a T2-FLAIR sequence, perpendicular to the hippocampus’s long axis, to obtain a three-dimensional region of interest. Radiomics were processed using Artificial Intelligence Kit software; logistic regression radiomics models were constructed. The model evaluation indexes included the area under the curve (AUC), accuracy, sensitivity, and specificity. ResultsThe respective AUC, accuracy, sensitivity, and specificity were 0.863, 81.4%, 78.0%, and 84.6% between the MRI − HS and HC groups in the training set and 0.855, 75.0%, 68.2%, and 81.8% in the test set; 0.975, 95.0%, 92.9%, and 98.0% between the MRI + HS and HC groups in the training set and 0.954, 88.7%, 90.0%, and 87.0% in the test set; and 0.912, 84.3%, 83.3%, and 86.5% between the MTLE and HC groups in the training set and 0.854, 79.7%, 80.8%, and 77.3% in the test set. The AUC values of the comparative radiomics models were > 0.85, indicating good diagnostic efficiency. ConclusionThe hippocampal radiomics models based on T2-FLAIR images can help diagnose MTLE with HS. They can be used as biological markers for MTLE diagnosis.