With the continuous improvement of medical imaging equipment, CT, MRI and PET images can obtain accurate anatomical information of the same patient site. However, due to the fuzziness of medical image physiological evaluation and the unhealthy understanding of objects, the registration effect of many methods is not ideal. Therefore, based on the medical image registration model of Partial Volume (PV) image interpolation method and rigid medical image registration method, this paper established the non-rigid registration model of maximum mutual information Novel Partial Volume (NPV) image interpolation method. The proposed NPV interpolation method uses the Davidon-Fletcher-Powell algorithm (DFP) algorithm optimization method to solve the transformation parameter matrix and realize the accurate transformation of the floating image. In addition, the cubic B-spline is used as the kernel function to improve the image interpolation, which effectively improves the accuracy of the registration image. Finally, the proposed NPV method is compared with the PV interpolation method through the human brain CT-MRI-PET image to obtain a clear CT-MRI-PET image. The results show that the proposed NPV method has higher accuracy, better robustness, and easier realization. The model should also have guiding significance in face recognition and fingerprint recognition.