The purpose of this work is to develop an automated landmark-guided deformable image registration (LDIR) algorithm between the planning CT and daily cone-beam CT (CBCT) with low image quality. This method uses an automated landmark generation algorithm in conjunction with a local small volume gradient matching search engine to map corresponding landmarks between the CBCT and the planning CT. The landmarks act as stabilizing control points in the following Demons deformable image registration. LDIR is implemented on graphics processing units (GPUs) for parallel computation to achieve ultra fast calculation. The accuracy of the LDIR algorithm has been evaluated on a synthetic case in the presence of different noise levels and data of six head and neck cancer patients. The results indicate that LDIR performed better than rigid registration, Demons, and intensity corrected Demons for all similarity metrics used. In conclusion, LDIR achieves high accuracy in the presence of multimodality intensity mismatch and CBCT noise contamination, while simultaneously preserving high computational efficiency.