Fully understanding the inner spatial structure of the nasal sinuses is necessary for mastering nasal sinus and skull base surgery. However, it is hard for medical students to have a whole picture of the sinuses using traditional educational methods. Immersive virtual reality (VR) systems have great potential as a supplement to anatomy education, yet few of them exist for theoretical anatomical knowledge of nasal sinuses. The purpose of this study was to investigate the usability of the immersive VR technology in nasal sinus anatomy education context among undergraduate medical students. Thus, an interactive nasal sinus anatomy learning system was developed and distributed in two versions: the immersive VR version and the non-immersive desktop-3D version. A total of 21 students were recruited for this study and were randomized into the VR group with HMD-based learning and the control group with desktop-based learning. The study gathered students’ perceptions regarding usability and side effects including workload and cybersickness. In addition, objective data regarding interaction efficiency were gathered for analysis. Results showed no difference was found in the overall usability scores between the VR version and the desktop-3D version of the system. The VR group perceived a higher level of performance than the control group. However, the VR group needed more support from a technical person to use the system and were more likely to get lost in the virtual environment when rotating the models. Overall, this study suggested that more natural and intuitive interactions need to be explored to exploit the potential of immersive VR in nasal sinus anatomy learning.