A mutual information-based non-rigid medical image registration algorithm is presented. An approximate function of Harming windowed sinc is used as kernel function of partial volume (PV)interpolation to estimate the joint histogram, which is the key to calculating the mutual information. And a new method is proposed to compute the gradient of mutual information with respect to themodel parameters. The transformation of object is modeled by a free-form deformation (FFD) based on B-splines. The experiments on 3D synthetic and real image data show that the algorithm can con-verge at the global optimum and restrain the emergency of local extreme.