BACKGROUND: Podoplanin (PDPN) is a membrane glycoprotein implicated in tumor invasion and immune modulation in high-grade gliomas (HGGs). However, the non-invasive prediction of PDPN expression and its prognostic significance using radiomics remains unexplored. MATERIALS AND METHODS: This study used preoperative contrast-enhanced MRI T1WI data analyzed by gradient boosting machine to predict podoplanin (PDPN) expression and overall survival (OS) in HGG patients. RESULTS: We retrospectively analyzed 89 HGG patients' clinical data, MRI images, and RNA-seq profiles from TCIA. For each patient, 107 radiomics features were extracted from HGG subregions. The radiomics prognostic model was built using two selected features, glcm_Idmn and glcn_Idn. Through validation with external the REMBRANDT dataset (n=39), the model demonstrated great predictive performance for the PDPN expression levels and OS in HGG. The area under the curve of the ROC in the radiomics signature combined with clinical risk factors for the 1-year, 2-year, and 3-year OS rates in the TCIA-HGG were 0.799, 0.883, and 0.923, respectively. Gradient boosting machine using preoperative MRI T1WI and extracted radiomics features performed well in predicting the expression of PDPN and OS in HGG. CONCLUSIONS: Radiomics features extracted from MRI images can non-invasively predict PDPN expression and prognosis in HGG, offering a potential imaging biomarker for individualized clinical management.