Abstract In this study, we tested and compared radiomics and deep learning-based approaches on the public LUNG1 dataset, for the prediction of 2-year overall survival (OS) in non-small cell lung cancer patients. Radiomic features were extracted from the gross tumor volume using Pyradiomics, while deep features were extracted from bi-dimensional tumor slices by convolutional autoencoder. Both radiomic and deep features were fed to 24 different pipelines formed by the combination of four feature selection/reduction methods and six classifiers. Direct classification through convolutional neural networks (CNNs) was also performed. Each approach was investigated with and without the inclusion of clinical parameters. The maximum area under the receiver operating characteristic on the test set improved from 0.59, obtained for the baseline clinical model, to 0.67 ± 0.03, 0.63 ± 0.03 and 0.67 ± 0.02 for models based on radiomic features, deep features, and their combination, and to 0.64 ± 0.04 for direct CNN classification. Despite the high number of pipelines and approaches tested, results were comparable and in line with previous works, hence confirming that it is challenging to extract further imaging-based information from the LUNG1 dataset for the prediction of 2-year OS.