Since the outbreak of COVID-19, it has spread to more than 160 countries, causing a pandemic worldwide, bringing a huge impact on the global medical system and causing huge economic losses. The genome of SARS-CoV-2 is constantly mutating, with higher immune escape ability and stronger infectivity, and the infected people tend to have mild symptoms, which brings greater challenge to epidemic prevention and control. The epidemic prevention and control in China has gone through four stages and achieved remarkable results, which proves the advanced and scientific nature of Chinese epidemic prevention and control mode. Rapid and powerful pathogen detection capabilities as well as rapid and precise epidemiological investigation capabilities are the magic weapons for the effective control of COVID-19 in China. In medical institutions, especially in designated hospitals for COVID-19, timely, efficient and standardized epidemiological investigation is the key to the prevention and control of COVID-19 in hospital. Precise epidemiological investigation is the premise and basis for the implementation of hierarchical management and control of epidemic-related populations and epidemic-related areas in the hospital, and is the gua rantee to prevent the spread of epidemic in hospital and prevent the non-combat reduction of medical personnel. Com pared with the epidemiological investigation of the social aspect, epidemiological investigation of COVID-19 epidemic in hospital has its particularity, it is necessary to conduct a more precise epidemiological investigation in a small area, not only prevent the spread of the epidemic, but also meet the medical needs of patients as much as possible. How to carry out epidemiological investigation of the epidemic in the hospital (in key areas) will form a new topic of epidemic prevention and control. In the hospital prevention and control of COVID-19, Xiangya Hospital of Central South University has always insisted on completing the epidemiological investigation of COVID-19 with its own strength under the guidance of the Center for Disease Control and Prevention, forming a Xiangya mode of in-hospital epidemiological investigation. This article introduces the significance, methods and investigators of COVID-19 in-hospital epidemiological investigation, as well as the challenge and prospect of healthcare-associated infection under the new situation based on Xiangya's experience in epidemiological investigations in hospitals.