In the Song Dynasty, the system of prevention, control and treatment of the plague was established and led by the governments at all levels, while other social forces worked as supplement. The central government was still the core that adopted various medical, economical, and political approaches to prevent and control the epidemic. Local officials were the grassroots forces for the prevention and control of the plague by helping the victims, treating patients, and strengthening social control. Medical doctors were the backbone of the epidemic prevention, most of them went to the disaster area to diagnose and treat patients, dispense medicines, publish medical prescriptions, and disseminate official medical knowledge. The attitudes of general public to the plague were extremely complex, and their anti-epidemic measures were multiple. Influenced by natural disaster and the war between the Song and Jin Dynasties, the epidemics in local, military and border areas increased significantly in the early Southern Song Dynasty. In the process of preventing and controlling the plague, in addition to continuing to take traditional relief measures, the Southern Song Dynasty paid great attention to medical knowledge. The effective measures not only controlled the spread of the epidemic and the disease, but also made great contributions to the development of plague prevention in China.