We investigated the influence of breathing motion on radiation therapy according to four- dimensional computed tomography (4D-CT) technology and indicated the registration of 4D-CT images was significant. The demons algorithm in two interpolation modes was compared to the FFD model algorithm to register the different phase images of 4D-CT in tumor tracking, using iodipin as verification. Linear interpolation was used in both mode 1 and mode 2. Mode 1 set outside pixels to nearest pixel, while mode 2 set outside pixels to zero. We used normalized mutual information (NMI), sum of squared differences, modified Hausdorff-distance, and registration speed to evaluate the performance of each algorithm. The average NMI after demons registration method in mode 1 improved 1.76% and 4.75% when compared to mode 2 and FFD model algorithm, respectively. Further, the modified Hausdorff-distance was no different between demons modes 1 and 2, but mode 1 was 15.2% lower than FFD. Finally, demons algorithm has the absolute advantage in registration speed. The demons algorithm in mode 1 was therefore found to be much more suitable for the registration of 4D-CT images. The subtractions of floating images and reference image before and after registration by demons further verified that influence of breathing motion cannot be ignored and the demons registration method is feasible.