Abstract: OBJECTIVE The prevention and control of COVID-19 remains in a severe situation, the nosocomial infection incidents happen occasionally, and it is an important measure to solve the difficulties encountered in prevention and control of the nosocomial infection and raise countermeasures so as to prevent the spread of COVID-19 epidemic in hospital. METHODS The countermeasures were proposed based on the difficulties in prevention and control of COVID-19 and related national rules as well as the practice in prevention and control. RESULTS The six difficulties encountered during the prevention and control, including the establishment of hospital emergency prevention and control organization system, the formulation of screening procedures, the allocation of medical supplies, treatment of fever patients, formulation of emergency treatment procedures and protection of frontline medical staff, were interpreted in the article, and the countermeasures were introduced. CONCLUSION In response to the prevention and control of the COVID-19, it is necessary for hospitals to establish the joint prevention and control mechanism as early as possible, optimize the original workflows for control of infection, solve the difficulties in the prevention and control and centralize the resources to conduct scientific, standardized and orderly prevention and control.