Information and knowledge，which are not only the foundation and important support, but also  a driving force in the process of risk assessment and decision-making, run through all stages of risk assessment and decision-making in the life cycle of major epidemics. Based on the characteristics of risk assessment and decision-making in major epidemics and related research, this paper explores the basic framework of collaborative mechanism of risk assessment and decision-making in major outbreaks, information aggregation mechanism and knowledge discovery platform, and constructs a flexible collaborative mechanism of risk assessment and decision-making of major epidemics. The mechanism takes the information aggregation mechanism and knowledge discovery platform as the key driving force, and the central matrix decision-making body organizational structure as the core component. It covers the whole process of event development, has certain flexibility, can fully mobilize the resources of all parties, and can achieve multi-sector and multi-agent collaborative and efficient cooperation. It provides support for the comprehensive prevention and control of the risk of major epidemics, effective response, prevention and resolution of major risks.