Abstract: Objective To explore the practice of infection prevention and control in non-designated three grade general hospital during COVID-19 epidemic period, further reduce the new coronavirus transmission risk, provide reference for epidemic prevention and control for non-designated hospitals. Methods Based on the diagnosis and treatment and prevention and control plan of the National Health Commission, combined with the actual situation of epidemic prevention and control in our city, the prevention and control strategy of non-designated general hospital infection was formulated from the establishment of hospital emergency prevention and control organization system, personnel and material reserves, multi-level and multi-channel training, formulation and update of system and process, multi department cooperation and district management. Results From January 22 to May 31, 2020, 467 165 outpatients and 8 346 fever outpatients were visited. There were 16 positive patients detected by nucleic acid test and sent to the designated hospital. During the novel coronavirus pneumonia epidemic, patients were screened and received for medical treatment. After training and guidance, the medical staff could effectively instruct and explain, and achieved zero detection, zero missing and zero cross infection. During this period, 54 working systems and processes were accumulated, which accumulated experience for dealing with public health emergencies in the future. Conclusion Novel coronavirus pneumonia is a severe epidemic situation. Under the situation of severe acute outbreak of coronavirus pneumonia, medical institutions should clearly define the division of labor through compacting responsibilities, establish and improve emergency response mechanisms, formulate system processes, implement feasible preventive and control measures, and think in many ways, intervene in various fields and cooperate in many departments, so that the spread and spread of the epidemic can be effectively prevented.