Abstract: Objective To explore the practical effects of the one hospital with multi-district model in major infectious diseases, and to explore how to maintain medical treatment capacity while dealing with major infectious diseases in comprehensive medical institutions in cities without public health centers. Methods Based on prefecture-level cities in Jiangsu province without public health centers, we analyzed the advantages, disadvantages and actual effects of coronavirus disease 2019(COVID-19) prevention and control in hospitals under the one hospital with multi-district model. Results During the COVID-19 pandemic, all the comprehensive designated hospitals in cities without public health centers in Jiangsu province took advantage of the one hospital with multi-district model and uniformly set isolation wards in relatively small districts. Conclusions During the prevention and control of major infectious diseases, for cities without public health centers, a single district of a comprehensive hospital under the one hospital with multi-district model can be quickly recruited and transformed into the treatment places for severe patients.