Since the outbreak of a new round of COVID-19 in Xi’an on December 9, 2021, the response capability of the city’s and even the province’s health system to major public health emergencies has been severely tested and challenged. Faced with the rapid spread of the Delta strain and its multiple hidden transmission chains, The First Affiliated Hospital of Xi’an Jiaotong University, as the largest comprehensive tertiary hospital in Northwest China, has successfully applied the 4R crisis management theory to prevent the pandemic spread and continue the clinic work as well. Balancing of epidemic prevention and medical service with scientific, orderly and standardized procedures has been achieved. Hence, we have contributed to the "The First Affiliated Hospital of Xi’an Jiaotong University model" for controlling the epidemic and restoring normal production and life as soon as possible under the guidance and command of the National Health Commission and provincial and municipal health administrative institutions at all levels. The First Affiliated Hospital of Xi’an Jiaotong University has improved the present management system and enhanced its management level amid epidemic prevention and control. This paper aims to provide new epidemic prevention experience under the changeable environment by explaining and summarizing our theoretical basis, operation mode and practical effects of our management system.