Digital Radiography (DR) image and digitally reconstructed radiography (DRR) image are different modality images, accurate and rapid multi-modality image registration is a technical difficulty. In practical applications, front and side DR and DRR images are generally acquired at same time. A multi-modality image registration algorithm is proposed based on combining mutual information and gradient information. Firstly, the low resolution images, which are got by wavelet transform, are registered based on particle swarm optimization (PSO) algorithm. And then, we can determine if the registration results are true. If it is not true, we don’t use it at the next process. Finally, we set the results of last process as initial position of Powell and register original images. The experimental results show that the algorithm can rapidly register multi-modality image, and the registration accuracy is 2 mm. The algorithm meets the practical application requirements.