Background:The early diagnosis of colorectal cancer (CRC) is associated with improved survival rates, and development of novel non-invasive, sensitive, and specific diagnostic tests is highly demanded. The objective of this paper was to identify commonly circulating microRNA (miRNA) biomarkers for use in CRC diagnosis. Methods: An artificial neural network (ANN) model was proposed in this work. Among miRNAs retrieved from the Gene Expression Omnibus dataset, four miRNAs with the best miRNA score were selected by ANN units. Results: The simulation results showed that the designed ANN model could accurately classify the sample data into cancerous or non-cancerous. Furthermore, based on the results of evaluated ANN model, the area under the ROC curve (AUC) of the designed ANN model as well as the regression coefficient between the output of the ANN and the expected output was one. The confusion matrix of the ANN model indicated that all non-cancerous patients were predicted as normal, and the cancerous patients as cancerous. Conclusion: Our findings suggest that the improved model can be used as a robust prediction toolbox for cancer diagnosis. In conclusion, by using ANN, circulatory miRNAs can be used as a non-invasive, sensitive and specific diagnostic marker.