To explore the connection between TGF-β1 expression and the survival of patients with head and neck squamous cell carcinoma (HNSCC), as well as whether non-invasive CT-based Radiomics can predict TGF-β1 expression in HNSCC patients. Data on transcriptional profiling and clinical information were acquired from the TCGA database and subsequently categorized based on the TGF-β1 expression cutoff value. Based on the completeness of enhanced arterial phase CT scans, 139 HNSCC patients were selected. The PyRadiomics package was used to extract radiomic features, and the 3D Slicer software was used for image segmentation. Using the mRMR_RFE and Repeat LASSO algorithms, the optimal features for establishing the corresponding gradient enhancement prediction models were identified. A survival analysis was performed on 483 patients, who were divided into two groups based on the TGF-β1 expression cut-off. The Kaplan-Meier curve indicated that TGF-β1 was a significant independent risk factor that reduced patient survival. To construct gradient enhancement prediction models, we used the mRMR_RFE algorithm and the Repeat_LASSO algorithm to obtain two features (glrlm and ngtdm) and three radiation features (glrlm, first order_10percentile, and gldm). In both the training and validation cohorts, the two established models demonstrated strong predictive potential. Furthermore, there was no statistically significant difference in the calibration curve, DCA diagram, or AUC values between the mRMR_RFE_GBM model and the LASSO_GBM model, suggesting that both models fit well. Based on these findings, TGF-β1 was shown to be significantly associated with a poor prognosis and to be a potential risk factor for HNSCC. Furthermore, by employing the mRMR_RFE_GBM and Repeat_LASSO_GBM models, we were able to effectively predict TGF-β1 expression levels in HNSCC through non-invasive CT-based Radiomics.