The registration method based on mutual information is currently a popular technique for the medical image registration, but the computation for the mutual information is complex and the registration speed is slow. In engineering process, a subsampling technique is taken to accelerate the registration speed at the cost of registration accuracy. In this paper a new method based on statistics sample theory is developed, which has both a higher speed and a higher accuracy as compared with the normal subsampling method, and the simulation results confirm the validity of the new method.