In recent years, major public health security incidents have occurred frequently around the world, testing the governance level and governance capabilities of various countries. Major public health and safety incidents can easily trigger various negative social emotions, which not only affect the mental health of social members, but also undermine the people’s feelings of good life to a certain extent. Taking the COVID-19 epidemic as an example, negative social emotions such as group panic, group anxiety, group anger, and group indifference have been prevalent for a long period of time, becoming unfavorable factors affecting social harmony and stability. Actively regulating negative social emotions caused by major public health events and strengthening the construction of social psychological service system are urgent needs to alleviate social conflicts, are important means of innovating social governance, and are also inevitable requirements for satisfying the people’s pursuit of a good life. Negative social emotions induced by major public health and safety incidents are large-scale and sustained, which formed after experiencing several important evolutionary stages such as emotional generation, emotional development, emotional outburst and emotional contagion under the dual effects of internal factors and external environment, having basic characteristics such as universality, specificity, explosiveness, and contagiousness. The internal motivations for the generation of negative emotions in major public health security incidents are expressed at four levels: social needs stimulate the arousal of negative social emotions; risk cognition promotes the differentiation of negative social emotions; psychological expectations promote the strengthening of negative social emotions; and herd mentality triggers the contagion of negative social emotions. The external effects of negative emotions generated in major public health and safety events are reflected in four aspects: the polarization effect of conflict of interests stimulating negative social emotions; the convergence effect of social justice inducing negative social emotions; the expectation effect of social prejudice strengthening negative social emotions; the diffusion effect of media communication triggering negative social emotions. Only by scientifically grasping the mechanisms and patterns of the generation of negative social emotions in major public health security incidents, strengthening social psychological guidance and humanistic care in major public health security incidents, and effectively regulating negative social emotions in major public health security incidents can we cultivate rational and peaceful people and ensure the sound and orderly development of the country’s social, political and economic development. Countermeasures to deal with negative social emotions in major public health security incidents include: paying close attention to people’s actual needs and blocking the sources of negative social emotions; promptly adjusting people’s risk perceptions and implementing isolation of negative social emotions; rationally guiding online emotional interactions to enhance the convergence of positive social emotions; fully guaranteeing the emotional support system and creating a positive social and emotional atmosphere.