To assess the degree and influencing factors of stigma of depression among residents in the urban center of Wuhan and to provide a relevant basis for alleviating the stigma of depression. Methods: One thousand community residents in the urban center of Wuhan were randomly selected by multi-stage stratified cluster, and general demographic data questionnaire and Depression Stigma Scale (DSS) were completed. Results: The detection rates of personal stigma and perceived stigma were 21.58% and 48.95%, respectively, for residents in the urban center of Wuhan. The total score of perceived stigma and 7 items were significantly higher than those of individual stigma (P<0.05). Age, education level, marital status, and mother’s education level significantly influenced personal stigma and perceived stigma (P<0.05). Religion and father’s educational level also influenced individual stigma (P<0.05). Gender and ethnicity had no significant relationship with personal stigma and perceived stigma (P>0.05). Conclusion: There is a certain degree of stigma toward depression among residents in the urban center of Wuhan. The stigma toward depression among the public is higher than that of individuals. Therefore, it is necessary to strengthen the popularization of depression knowledge to alleviate the discrimination of the public against depression and the stigma of individuals against depression.