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Colorectal cancer (CRC) is a form of cancer that impacts both the rectum and colon. Typically, it begins with a small abnormal growth known as a polyp, which can either be non-cancerous or cancerous. Therefore, early detection of colorectal cancer as the second deadliest cancer after lung cancer, can be highly beneficial. Moreover, the standard treatment for locally advanced colorectal cancer, which is widely accepted around the world, is chemoradiotherapy. Then, in this study, seven artificial intelligence models including decision tree, K-nearest neighbors, Adaboost, random forest, Gradient Boosting, multi-layer perceptron, and convolutional neural network were implemented to detect patients responder and non-responder to radiochemotherapy. For finding the potential predictors (genes), three feature selection strategies were employed including mutual information, F-classif, and Chi-Square. Based on feature selection models, four different scenarios were developed and five, ten, twenty and thirty features selected for designing a more accurate classification paradigm. The results of this study confirm that random forest, Gradient Boosting, decision tree, and K-nearest neighbors provided more accurate results in terms of accuracy, by 93.8%. Moreover, Among the feature selection methods, mutual information and F-classif showed the best results, while Chi-Square produced the worst results. Therefore, the suggested artificial intelligence models can be successfully applied as a robust approach for classification of colorectal cancer response to radiochemotherapy for medical studies., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)