We developed and validated novel radiomics-based nomograms to identify epidermal growth factor receptor (EGFR) mutations and the Ki-67 proliferation index of non-small cell lung cancer.We enrolled 132 patients with histologically verified non-small cell lung cancer from four hospital institutions who underwent computed tomography (CT) scans. EGFR mutations and the Ki-67 proliferation index were measured from tumor tissues. A total of 1,287 radiomic features were extracted, and a three-stage feature selection method was implemented to acquire the most valuable radiomic features. Finally, the radiomic scores and nomograms of the two tasks were established and tested. Receiver operating characteristic curves, calibration curves, and decision curves were used to evaluate their prediction performance and clinical utility.In task [1], smoking status and histological type were significantly associated with EGFR mutations. After feature selection, 10 features were used to establish radiomic score, which showed good performance [area under the curve (AUC) =0.800] in the validation cohort. The radiomic nomogram had an AUC of 0.798 (95% CI: 0.664 to 0.931) with a C-index of 0.798 in the validation cohort. In task [2], gender, smoking status, histological type, and stage showed a significant correlation with Ki-67 proliferation index expression. A total of 28 features were selected to develop a radiomic score, with an AUC of 0.820 in the validation cohort. The final nomogram showed an AUC of 0.828 (95% CI: 0.703 to 0.953) with a C-index of 0.828 in the validation cohort.EGFR mutations and Ki-67 proliferation index in non-small cell lung cancer can be predicted efficiently by the novel radiomic scores and nomograms.2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.