In recent times, as the healthcare system becomes more informational, the importance of patient privacy protection increases, making it necessary to identify factors that affect the perception of patient privacy protection. This study aimed to evaluate the relationship between nursing professionalism and the perception of patient privacy protection and the mediating role of nursing informatics competency. The study recruited 242 nursing students who had experienced dealing with patient information during clinical practice. The mediating model using the Hayes’ PROCESS macro (Model 4) was employed to test the study hypothesis. Nursing professionalism was found to be positively and significantly associated with the perception of patient privacy protection (β = 0.09, p = 0.021) with the mediation of nursing informatics (β = 0.18, p < 0.001). Our findings showed that nursing professionalism and nursing informatics competency determined the perception of patient privacy protection. The mediating role of nursing informatics competency implies that curricula designed to enhance nursing informatics competency of nursing students may increase their perception of patient privacy protection.