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Background: Predicting the mutation statuses of 2 essential pathogenic genes [epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (KRAS)] in non-small cell lung cancer (NSCLC) based on CT is valuable for targeted therapy because it is a non-invasive and less costly method. Although deep learning technology has realized substantial computer vision achievements, CT imaging being used to predict gene mutations remains challenging due to small dataset limitations. Methods:We propose a multi-channel and multi-task deep learning (MMDL) model for the simultaneous prediction of EGFR and KRAS mutation statuses based on CT images. First, we decomposed each 3D lung nodule into 9 views. Then, we used the pre-trained inception-attention-resnet model for each view to learn the features of the nodules. By combining 9 inception-attention-resnet models to predict the types of gene mutations in lung nodules, the models were adaptively weighted, and the proposed MMDL model could be trained end-to-end. The MMDL model utilized multiple channels to characterize the nodule more comprehensively and integrate patient personal information into our learning process. Results:We trained the proposed MMDL model using a dataset of 363 patients collected by our partner hospital and conducted a multi-center validation on 162 patients in The Cancer Imaging Archive (TCIA) public dataset. The accuracies for the prediction of EGFR and KRAS mutations were, respectively, 79.43% and 72.25% in the training dataset and 75.06% and 69.64% in the validation dataset. Conclusions:The experimental results demonstrated that the proposed MMDL model outperformed the latest methods in predicting EGFR and KRAS mutations in NSCLC.