Objective To correct the registration error and deformation of the combined PET/CT scanner. Methods This paper proposed an elastic registration method based on multi-transformation and multi-optimizer by using mutual information as metric. This method adopted rigid transformation firstly to ensure the global registration with simplex optimizer and then used BSpline FFD with limited memory Broyden Fietcher Goldfarb Shanno bound（LBFGSB）optimizer. This novel method was compared with those methods based on single transformation and single optimizer through testing six image pairs of three patients under combined PET/CT scanner. Results The mean registration time of the proposed method was 19.78s and the mean value of mutual information was 0.3115,which was better than those methods based on single transformation and single optimizer. Conclusions The proposed method based on multi-transformation and multi-optimizer could handle the deformation and the registration error caused by respiratory and organ motion in the combined scanner images and was superior to other traditional methods in speed and accuracy.