Background This study aimed to develop and validate radiomics-based nomograms for the identification of EGFR mutations in non-small cell lung cancer (NSCLC).Methods A retrospective analysis was performed on 313 NSCLC patients, who were randomly divided into training (n = 250) and validation (n = 63) groups. Radiomic features were extracted from 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and thin-section computed tomography (CT) scans. After selecting optimal radiomic features, four machine learning algorithms, including logistic regression (LR), random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGBoost), were used to develop and validate radiomics models. A combined model, incorporating the Rad score from the best performing radiomics model with clinical and radiological features, was then formulated. Finally, the integrated nomogram was generated. Its predictive performance and clinical utility were evaluated using receiver operating characteristic curves, calibration curves, and decision curve analysis.Results Among the radiomics models, the RF model showed the best performance with AUCs of 0.785 (95% CI, 0.726-0.844) and 0.776 (95% CI, 0.662-0.889) in the training and validation groups, respectively. The AUCs of the clinical and radiological models in both groups were 0.711 (95% CI, 0.645-0.776) and 0.758 (95% CI, 0.627-0.890), and 0.632 (95% CI, 0.564-0.699) and 0.677 (95% CI, 0.531-0.822), respectively. The combined model achieved the highest AUCs of 0.872 (95% CI, 0.829-0.915) and 0.831 (95% CI, 0.723-0.940) in the training and validation groups, respectively. The DeLong test confirmed the superiority of the combined model over the other three models. Both the calibration curve and the DCA indicated that the radiomics nomogram was consistent and clinically useful.Conclusions Radiomics combined with machine learning and based on 18F-FDG PET/CT images can effectively determine EGFR mutation status in NSCLC patients. Radiomics-based nomograms provide a non-invasive and visually intuitive prediction tool for screening NSCLC patients with EGFR mutations in a clinical setting.