The change from "acquaintance society" to "stranger society" is an inevitable trend of social progress and development. The sudden outbreak of a major epidemic has caused not only significant losses to the politics, economy, culture, and health of China and the international community, but also a huge impact on the public psychology in the stranger society. From the perspective of public mentality, this article believes that the emptiness of daily experience in strangers' society, information overload, worries about future uncertainties, and emotional infections among individuals and groups, etc., have caused public's negative emotions such as anxiety, fear, and hypothesis. The indifference, rejection, suspicion, and lack of trust in the stranger society will further aggravate the generation of negative emotions during the epidemic, even trigger irrational behaviors, and bring severe challenges to epidemic prevention and control. Based on this, this article proposes countermeasures from the macro, meso, and micro levels for negative emotions of strangers in the major social epidemic.