Non-anatomical resections of liver tumors can be very challenging as the surgeon cannot use anatomical landmarks on the liver surface or in the ultrasound image for guidance. This makes it difficult to achieve negative resection margins (R0) and still preserve as much healthy liver tissue as possible. Even though image-guided surgery systems have been introduced to overcome this challenge, they are still rarely used due to their inaccuracy, time-effort and complexity in usage and setup. Methods: We have developed a novel approach, which allows us to create an intra-operative resection plan using navigated ultrasound. First, the surface is scanned using a navigated ultrasound, followed by tumor segmentation on a midsection ultrasound image. Based on this information, the navigation system calculates an optimal resection strategy and displays it along with the tracked surgical instruments. In this study, this approach was evaluated by three experienced hepatobiliary surgeons on ex-vivo porcine models. Results: Using this technique, an R0 resection could be achieved in 22 out of 23 (95.7% R0 resection rate) cases with a median resection margin of 5.9 mm (IQR 3.5–7.7 mm). The resection margin between operators 1, 2 and 3 was 7.8 mm, 4.15 mm and 5.1 mm respectively (p = 0.054). Conclusions: This approach could represent a useful tool for intra-operative guidance in non-anatomical resection alongside conventional ultrasound guidance. However, instructions and training are essential especially if the operator has not used an image-guidance system before.