Three-dimensional x-ray cone-beam CT (CBCT) is being increasingly used in radiation therapy. Since the whole treatment course typically lasts several weeks, the repetitive x-ray imaging results in large radiation dose delivered on the patient. In the current radiation therapy treatment, CBCT is mainly used for patient set-up, and a rigid transformation of the CBCT data from the planning CT data is also assumed. For an accurate rigid registration, it is not necessary to acquire a full 3D image. In this paper, we propose a patient set-up protocol based on partially blocked CBCT. A sheet of lead strips is inserted between the x-ray source and the scanned patient. From the incomplete projection data, only several axial slices are reconstructed and used in the image registration for patient set-up. Since the radiation is partially blocked, the dose delivered onto the patient is significantly reduced, with an additional benefit of reduced scatter signals. The proposed approach is validated using experiments on two anthropomorphic phantoms. As x-ray beam blocking ratio increases, more dose reduction is achieved, while the patient set-up error also increases. To investigate this tradeoff, two lead sheets with different strip widths are implemented, which correspond to radiation dose reduction of ~6 and ~11, respectively. We compare the registration results using the partially blocked CBCT with those using the regular CBCT. Both lead sheets achieve high patient set-up accuracies. It is seen that, using the lead sheet with radiation dose reduction by a factor of ~11, the patient set-up error is still less than 1mm in translation and less than 0.2 degrees in rotation. The comparison of the reconstructed images also shows that the image quality of the illuminated slices in the partially blocked CBCT is much improved over that in the regular CBCT.