High Intensity Focused Ultrasound (HIFU) has been successfully applied in tumor therapy. For a successful HIFU therapy, it is crucial to localize the tumor region accurately. In this paper, we present a semi-automatic non-rigid registration method for implementing image guided surgery navigation and localization by matching pre-operative CT/MR images and intra-operative ultrasound images. The global motion of the target is modeled by an affine transformation, while the local deformation of the target is described by Free-Form Deformation (FFD) based on B-splines. The results of our experiments on simulated and real data show that the non-rigid registration method based on HPV interpolation (partial volume based on the Hanning windowed sinc function) is effective at restraining local extrema and improves the accuracy of registration results. A preliminary clinical validation of the use of the non-rigid registration method in image guided localization of a HIFU system is also reported.