This study aimed to evaluate the performance of the hybrid deformable image registration (DIR) method in comparison with intensity-based DIR for pelvic cone-beam computed tomography (CBCT) images, using intensity and anatomical information. Ten prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) were studied. Nine or ten CBCT scans were performed for each patient. First, rigid registration was performed between the planning CT and all CBCT images using gold fiducial markers, and then DIR was performed. The Dice similarity coefficient (DSC) and center of mass (COM) displacement were used to evaluate the quantitative DIR accuracy. The average DSCs for intensity-based DIR for the prostate, rectum, bladder, and seminal vesicles were 0.84 ± 0.05, 0.75 ± 0.05, 0.69 ± 0.07 and 0.65 ± 0.11, respectively, whereas those values for hybrid DIR were 0.98 ± 0.00, 0.97 ± 0.01, 0.98 ± 0.00 and 0.94 ± 0.03, respectively (P < 0.05). The average COM displacements for intensity-based DIR for the prostate, rectum, bladder, and seminal vesicles were 2.0 ± 1.5, 3.7 ± 1.4, 7.8 ± 2.2 and 3.6 ± 1.2 mm, whereas those values for hybrid DIR were 0.1 ± 0.0, 0.3 ± 0.2, 0.2 ± 0.1 and 0.6 ± 0.6 mm, respectively (P < 0.05). These results showed that the DSC for hybrid DIR had a higher DSC value and smaller COM displacement for all structures and all patients, compared with intensity-based DIR. Thus, the accumulative dose based on hybrid DIR might be trusted as a high-precision dose estimation method that takes into account organ movement during treatment radiotherapy.