In this paper we present a new approach for the non-rigid registration of multi-modality images. Our approach is based on an information theoretic measure called the cumulative residual entropy (CRE), which is a measure of entropy defined using cumulative distributions. Cross-CRE between two images to be registered is defined and maximized over the space of smooth and unknown non-rigid transformations. For efficient and robust computation of the non-rigid deformations, a tri-cubic B-spline based representation of the deformation function is used. The key strengths of combining CCRE with the tri-cubic B-spline representation in addressing the non-rigid registration problem are that, not only do we achieve the robustness due to the nature of the CCRE measure, we also achieve computational efficiency in estimating the non-rigid registration. The salient features of our algorithm are: (i) it accommodates images to be registered of varying contrast+brightness, (ii) faster convergence speed compared to other information theory-based measures used for non-rigid registration in literature, (iii) analytic computation of the gradient of CCRE with respect to the non-rigid registration parameters to achieve efficient and accurate registration, (iv) it is well suited for situations where the source and the target images have field of views with large non-overlapping regions. We demonstrate these strengths via experiments on synthesized and real image data.