Introduction: The novel corona-virus outbreak three years ago has changed people’s lives, with different responses around the world. As the largest developing country, China has taken strict prevention and control measures against this endemic. Although it is not very convenient, people have been used to such prevention and control methods. In December, 2022, China changed the prevention and control measures, a large number of patients were infected in a short period of time. Outpatient department acted as the first line of the hospital, and outpatient nurses acted as fighters, facing great difficulties and psychological pressure.In-depth understanding of the real experience of outpatient nurses after the change of COVID-19 prevention and control measures in China will provide reference for further improving the management level of emergency nursing. Methods: From December 2022 to January 2023, in the initial stage of the change of endemic prevention measures, 16 outpatient nurses from the First Affiliated Hospital of Soochow University conducted semi-structured interviews, and analyzed the interview data by Colaizzi analysis. Results: Based on the real experience of 16 outpatient nurses in this special period, four themes were extracted. The themes were the following:(1)Ethical challenges; (2)Changes in life; (3)Get experience, normalize, and adapt to the endemic; (4)Re-understanding for work and life. The suggestions were the following:(1)Pay more attention to the emotional changes of the outpatient nurses, and give them psychological support; (2)Strengthen the social support system and provide good logistics support; (3)Improve the management system, and pay attention to the suggestions and reflections of medical staff. Conclusion: Through this interview, it was discovered that outpatient nurses demonstrated a strong sense of responsibility and mission during the process of epidemic prevention policy changes. However, they also experienced negative psychological effects due to inadequate understanding of the disease, heavy treatment tasks, and risk of self-infection. Therefore, managers should optimize human resource allocation, promptly alleviate negative emotions among outpatient nurses, and provide them with psychological counseling services.