To develop and validate a general radiomics nomogram capable of identifying EGFR mutation status in non-small cell lung cancer (NSCLC) patients, regardless of patient with either contrast-enhanced CT (CE-CT) or non-contrast-enhanced CT (NE-CT).A total of 412 NSCLC patients were retrospectively enrolled in this study. Patients' radiomics features not significantly different between NE-CT and CE-CT were defined as general features, and were further used to construct the general radiomics signature. Fivefold cross-validation was used to select the best machine learning algorithm. Finally, a general radiomics nomogram was developed using general radiomics signature, and clinical and radiological characteristics. Two groups of data collected at different time periods were used as two test sets to access the discrimination and clinical usefulness. Area under the receiver operating characteristic curve (ROC-AUC) was applied to performance evaluation.The general radiomics signature yielded the highest AUC of 0.756 and 0.739 in the two test sets, respectively. When applying to same type of CT, the performance of general radiomics signature was always similar to or higher than that of models built using only NE-CT or CE-CT features. The general radiomics nomogram combining general radiomics signature, smoking history, emphysema, and ILD achieved higher performance whether applying to NE-CT or CE-CT (test set 1, AUC = 0.833 and 0.842; test set 2, AUC = 0.839 and 0.850).Our work demonstrated that using general features to construct radiomics signature and nomogram could help identify EGFR mutation status of NSCLC patients and expand its scope of clinical application.• General features were proposed to construct general radiomics signature using different types of CT of different patients at the same time to identify EGFR mutation status of NSCLC patients. • The general radiomics nomogram based on general radiomics signature, and clinical and radiological characteristics could identify EGFR mutation status of patients with NSCLC and outperformed the general radiomics signature. • The general radiomics nomogram had a wider scope of clinical application; no matter which of NE-CT and CE-CT the patient has, its EGFR mutation status could be predicted.© 2021. The Author(s).