RATIONALE AND OBJECTIVES Image registration in magnetic resonance (MR) image-guided liver therapy enhances surgical guidance by fusing preoperative multimodality images with intraoperative images, or by fusing intramodality images to correlate serial intraoperative images to monitor the effect of therapy. The objective of this paper is to describe the application of navigator echo and projection profile matching to fast two-dimensional image registration for MR-guided liver therapy. MATERIALS AND METHODS We obtain navigator echoes along the read-out and phase-encoding directions by using modified gradient echo imaging. This registration is made possible by masking out the liver profile from the image and performing profile matching with cross-correlation or mutual information as similarity measures. The set of experiments include a phantom study with a 2.0-T experimental MR scanner, and a volunteer and a clinical study with a 0.5-T open-configuration MR scanner, and these evaluate the accuracy and effectiveness of this method for liver therapy. RESULTS Both the phantom and volunteer study indicate that this method can perform registration in 34 ms with root-mean-square error of 1.6 mm when the given misalignment of a liver is 30 mm. The clinical studies demonstrate that the method can track liver motion of up to approximately 40 mm. Matching profiles with cross-correlation information perform better than with mutual information in terms of robustness and speed. CONCLUSION The proposed image registration method has potential clinical impact on and advantages for MR-guided liver therapy.