Objective: To observe the application effect of “online + offline” mixed teaching mode in clinical nursing teaching. Methods: A total of 72 clinical nursing workers, who work in PLA General Hospital and participated in the experiment from March 2019 to March 2021, were selected as the subjects of this study. According to the odd numbers assigned to the participants’ names, the participants were divided into two groups: the experimental group and the control group, with 36 cases in each group. The experimental group received “online + offline” hybrid teaching, whereas the control group received traditional offline teaching. In order to evaluate the efficacy and safety of the two groups of nursing workers, their assessment scores, teaching satisfaction scores, and teaching evaluation indicators were observed. Results: The experimental group was significantly better than the control group in terms of assessment scores, teaching satisfaction scores, and teaching evaluation indicators (P < 0.05). Conclusion: In clinical nursing teaching, the “online + offline” mixed teaching mode plays a unique role in improving students’ scores and teaching quality; thus, it should be promoted.