Purpose The overexpression of aquaporin-1 (AQP1) is associated with poor prognosis in rectal cancer. This study aimed to explore the value of multi-parameter diffusion and perfusion MRI and radiomics models in predicting AQP1 high expression. Methods This prospective study was performed from July 2019 to February 2021, which included rectal cancer participants after preoperative rectal MRI, with diffusion-weighted imaging, intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), and dynamic contrast-enhanced (DCE) sequences. Radiomic features were extracted from MR images, and immunohistochemical tests assessed AQP1 expression. Selected quantitative MRI and radiomic features were analyzed. Receiver operating characteristic (ROC) curves evaluated the predictive performance. The nomogram performance was evaluated by its calibration, discrimen, and clinical utility. The intraclass correlation coefficient evaluated the interobserver agreement for the MRI features. Results 110 participants with the age of 60.7 +/- 12.5 years been enrolled in this study. The apparent diffusion coefficient (ADC), IVIM_D, DKI_diffusivity, and DCE_Ktrans were significantly higher in participants with high AQP1 expression than in those with low expression (P < 0.05). ADC (b =1000, 2000, and 3000 s/mm 2 ), IVIM_D, DKI_diffusivity, and DCE_Ktrans were positively correlated (r = 0.205, 0.275, 0.37, 0.235, 0.229, and 0.227, respectively; P < 0.05), whereas DKI_Kurtosis was negatively correlated (r= -0.22, P=0.021) with AQP1 expression. ADC (b =3000 s/mm(2)), IVIM_D, DKI_ diffusivity, DKI_Kurtosis, and DCE_Ktrans had moderate diagnostic efficiencies for high AQP1 expression (AUC= 0.715, 0.636, 0.627, 0.633, and 0.632, respectively; P<0.05). The radiomic features had excellent predictive efficiency for high AQP1 expression (AUC =0.967 and 0.917 for training and validation). The model-based nomogram had C-indexes of 0.932 and 0.851 for the training and validation cohorts, which indicated good fitting to the calibration curves (p> 0.05). Conclusion Diffusion and perfusion MRI can indicate the aquaporin-1 expression in rectal cancer, and radiomic features can enhance the predictive efficiency for high AQP1 expression. A nomogram for high aquaporin-1 expression will improve clinical decision-making. [GRAPHICS] .