Purpose To evaluate feasibility of automatic software-based path proposals for CT-guided percutaneous biopsies. Methods Thirty-three patients (60  ±  12 years) referred for CT-guided biopsy of focal liver lesions were consecutively included. Pre-interventional CT and dedicated software (FraunhoferMeVis Pathfinder) were used for (semi)automatic segmentation of relevant structures. The software subsequently generated three path proposals in downward quality for CT-guided biopsy. Proposed needle paths were compared with consensus proposal of two experts (comparable, less suitable, not feasible). In case of comparable results, equivalent approach to software-based path proposal was used. Quality of segmentation process was evaluated (Likert scale, 1  =  best, 6  =  worst), and time for processing was registered. Results All biopsies were performed successfully without complications. In 91 % one of the three automatic path proposals was rated comparable to experts’ proposal. None of the first proposals was rated not feasible, and 76 % were rated comparable to the experts’ proposal. 7 % automatic path proposals were rated not feasible, all being second choice ( n = 1 ) or third choice ( n = 6 ). In 79 %, segmentation at least was good. Average total time for establishing automatic path proposal was 42  ±  9 s. Conclusion Automatic software-based path proposal for CT-guided liver biopsies in the majority provides path proposals that are easy to establish and comparable to experts’ insertion trajectories.