Non-rigid medical image registration based on mutual information often leads to unreasonable deformation due to the lack of geometric space constraints in images. We therefore propose a non-rigid medical image registration method combining bending energy and corresponding constraints of landmarks. In order to restrain the unreasonable deformation of soft tissues in medical images, two regular terms including bending energy penalty and Euclidean distance between corresponding landmarks are added in the mutual information registration target function. The image registration results of brain MRI, head and neck CT and chest CBCT show that this method can improve the quality of registration effectively.