AIM: This study aimed to create and validate a clinic-radiomics nomogram based on computed tomography (CT) imaging for predicting preoperative perineural invasion (PNI) of rectal cancer (RC). MATERIAL AND METHODS: This study enrolled 303 patients with RC who were divided into training (n = 242) and test datasets (n = 61) in an 8:2 ratio with all their clinical outcomes. A total of 3,296 radiomic features were extracted from CT images. Five machine learning (ML) models (logistic regression (LR)/K-nearest neighbor (KNN)/multilayer perceptron (MLP)/support vector machine (SVM)/light gradient boosting machine (LightGBM)) were developed using radiomic features derived from the arterial and venous phase images, and the model with the best diagnostic performance was selected. By combining the radiomics and clinical signatures, a fused nomogram model was constructed. RESULTS: After using the Mann-Whitney U-test and least absolute shrinkage and selection operator (LASSO) to remove redundant features, the MLP model proved to be the most efficient among the five ML models. The fusion nomogram based on MLP prediction probability further improves the ability to predict the PNI status. The area under the curve (AUC) of the training and test sets was 0.883 and 0.889, respectively, which were higher than those of the clinical (training set, AUC = 0.710; test set, AUC = 0.762) and radiomic models (training set, AUC = 0.840; test set, AUC = 0.834). CONCLUSIONS: The clinical-radiomics combined nomogram model based on enhanced CT images efficiently predicted the PNI status of patients with RC.