Background: To investigate the mental health status of Chinese residents during the epidemic of COVID-19 and identify the positive and negative factors affecting mediating effects of negative cognitive processing bias on mental health. Methods: Using a general questionnaire, such as the self-rating depression scale, the state anxiety inventory, and the negative cognitive processing bias questionnaire, an internet-based survey was conducted on 60199 residents in China. An ordered multiple logistic regression analysis model was used to analyze the collected data. Results: The survey showed that the incidences of mild, moderate, and severe depression were 62.65%, 11.33%, and 6.14%, respectively, and that of mild, moderate and severe anxiety were 33.21%, 41.27%, and 22.99%, respectively. The results of ordered multiple logistic regression analysis showed that factors, such as female gender, age more than 55 years elderly, high school education level, medical staff, marital conflicts, negative attention bias, rumination, and death rate positively affected the level of depression and anxiety. The good family functionality, democratic working atmosphere, and a myriad of social activities negatively affected the level of depression and anxiety.Conclusion: The Chinese residents exhibited a high prevalence of anxiety and depression during the epidemic. Thus, psychological interventions should focus on the vulnerable groups, and cognitive training should focus on reducing the negative cognitive processing bias that might be an effective way to alleviate the mental stress of the general public during the COVID-19 pandemic.