Prostate cancer is the most common tumor site treated with intensity modulated radiation therapy (IMRT). However, due to patient and organ motions, treatment-induced physiological changes, and different daily filling in the bladder and rectum, the position of the prostate in relation to the fixed pelvic bone can change significantly. Without a reliable guiding technique, this could result in underdosing the target and overdosing the critical organs. Therefore, image-guided localization of the prostate must be performed prior to each treatment, which led to the development of a new radiation treatment modality, the image-guided radiation therapy (1GRT). One form of IGRT is to implant three gold seed markers into the prostate gland to serve as a fixed reference system. Daily patient setup verification is performed by using the gold seed markers-based image registration rather than the commonly used bony landmarks-based approach. In this paper, we present an efficient and automated method for registering digitally reconstructed radiographs (DRR) and kV X-ray images of the prostate with high accuracy using a hybrid method. Our technique relies on both internal fiducial markers (i.e. gold seed markers) implanted into the prostate and a robust, hybrid 2D registration method using a salient-region based image registration technique. The registration procedure consists of several novel steps. Validation experiments were performed to register DRR and kV X-ray images in anterior-posterior (AP) or lateral views and the results were reviewed by experienced radiation oncology physicists.