ABSTRACT: OBJECTIVE:To retrospectively assess the effect of CT slice thickness on the reproducibility of radiomic features (RFs) of lung cancer, and to investigate whether convolutional neural network (CNN)-based super-resolution (SR) algorithms can improve the reproducibility of RFs obtained from images with different slice thicknesses. MATERIALS AND METHODS:CT images with 1-, 3-, and 5-mm slice thicknesses obtained from 100 pathologically proven lung cancers between July 2017 and December 2017 were evaluated. CNN-based SR algorithms using residual learning were developed to convert thick-slice images into 1-mm slices. Lung cancers were semi-automatically segmented and a total of 702 RFs (tumor intensity, texture, and wavelet features) were extracted from 1-, 3-, and 5-mm slices, as well as the 1-mm slices generated from the 3- and 5-mm images. The stabilities of the RFs were evaluated using concordance correlation coefficients (CCCs). RESULTS:The mean CCCs for the comparisons of original 1 mm vs. 3 mm, 1 mm vs. 5 mm, and 3 mm vs. 5 mm images were 0.41, 0.27, and 0.65, respectively (p < 0.001 for all comparisons). Tumor intensity features showed the best reproducibility while wavelets showed the lowest reproducibility. The majority of RFs failed to achieve reproducibility (CCC ? 0.85; 3.6%, 1.0%, and 21.5%, respectively). After applying the CNN-based SR algorithms, the reproducibility significantly improved in all three pairings (mean CCCs: 0.58, 0.45, and 0.72; p < 0.001 for all comparisons). The reproducible RFs also increased (36.3%, 17.4%, and 36.9%, respectively). CONCLUSION:The reproducibility of RFs in lung cancer is significantly influenced by CT slice thickness, which can be improved by the CNN-based SR algorithms.