Medical image registration is the key technology in image guided radiation therapy (IGRT) systems. On the basis of the previous work on our IGRT prototype with a biorthogonal x-ray imaging system, we described a method focused on the 2D/2D rigid-body registration using multiresolution pyramid based mutual information in this paper. Three key steps were involved in the method ： firstly, four 2D images were obtained including two x-ray projection images and two digital reconstructed radiographies（DRRs ） as the input for the registration ； Secondly, each pair of the corresponding x-ray image and DRR image were matched using multiresolution pyramid based mutual information under the ITK registration framework ； Thirdly, we got the final couch offset through a coordinate transformation by calculating the translations acquired from the two pairs of the images. A simulation example of a parotid gland tumor case and a clinical example of an anthropomorphic head phantom were employed in the verification tests. In addition, the influence of different CT slice thickness were tested. The simulation results showed that the positioning errors were 0.068±0.070, 0.072±0.098, 0.154±0.176mm along three axes which were lateral, longitudinal and vertical. The clinical test indicated that the positioning errors of the planned isocenter were 0.066, 0.07, 2.06mm on average with a CT slice thickness of 2.5mm. It can be concluded that our method with its verified accuracy and robustness can be effectively used in IGRT systems for patient setup.