To predict the volume change of stage III NSCLC after radiotherapy with 60 Gy. This retrospective study included two independent cohorts, a train cohort of 192 patients, and a test cohort of 31 patients. We developed a radiomics model based on radiomics features and clinical variables. LIFEx package was used to extract radiomics texture features from CT images. The classification method was logistic regression analysis and feature selection was performed by correlation coefficients. Performance metrics of logistic regression include accuracy, precision, the receiver operating characteristic curves, and recall. The combination features of clinical variables and radiomics can predict the tumor volume change after radiotherapy with 88.7% accuracy (88.6% precision, 88.7% recall, and 88.7% ROC area). Radiomics features combined with medical knowledge have a great potential to predict accurately tumor volume change of stage III NSCLC after radiotherapy with 60 Gy. © The Author(s) 2021.