Background The implementation of intraoperative navigation in liver surgery is handicapped by intraoperative organ shift, tissue deformation, the absence of external landmarks, and anatomical differences in the vascular tree. To investigate the impact of surgical manipulation on the liver surface and intrahepatic structures, we conducted a prospective clinical trial. Methods Eleven consecutive patients [4 female and 7 male, median age = 67 years (range = 54-80)] with malignant liver disease [colorectal metastasis (n = 9) and hepatocellular cancer (n = 2)] underwent hepatic resection. Pre-and intraoperatively, all patients were studied by CT-based 3D imaging and assessed for the potential value of computer-assisted planning. The degree of liver deformation was demonstrated by comparing pre-and intraoperative imaging. Results Intraoperative CT imaging was successful in all patients. We found significant deformation of the liver. The deformation of the segmental structures is reflected by the observed variation of the displacements. There is no rigid alignment of the pre-and intraoperative organ positions due to overall deflection of the liver. Locally, a rigid alignment of the anatomical structure can be achieved with less than 0.5 cm discrepancy relative to a segmental unit of the liver. Changes in total liver volume range from -13 to ?24%, with an average absolute difference of 7%. Conclusions These findings are fundamental for further development and optimization of intraoperative navigation in liver surgery. In particular, these data will play an important role in developing automation of intraoperative continuous registration. This automation compensates for liver shift during surgery and permits real-time 3D visualization of navigation imaging.