Explore the influence of fear of COVID-19 on depression, with anxiety as a mediator and perceived social support and stress perception as moderates. From February to March 2020, 1,196 valid data were collected online through questionnaire by cluster sampling method. Fear of COVID-19 Questionnaire, the Patient Health Questionnaire 9-Item Scale (PHQ-9), the Generalized Anxiety Disorder 7-Item Scale (GAD-7), the Perceived Social Support Scale (PSSS) and the10-item Perceived Stress Scale (PSS-10) were used as the survey instrument, and the participants were female undergraduates from a liberal arts college of a Chinese university. Common method bias was assessed using Harman's single-factor test in SPSS and confirmatory factor analysis in AMOS. The levels of participants' anxiety, depression and perceived social support were described using frequency and percentage, Pearson Correlation test was used to measure the correlation between the variables. The PROCESS macro for SPSS (Model 1, Model 4, and Model 21) were applied to examine the mediating effect and moderating effect of the model. Fear of COVID-19 can positively influence depression, anxiety plays a mediating role between fear of COVID-19 and depression, perceived social support negatively moderates the relationship between fear of COVID-19 and anxiety, and stress perception positively moderates the relationship between anxiety and depression. These five variables can form a moderated mediating effect model. Fear of COVID-19, anxiety and stress perception are risk factors for depression, perceived social support is a protective factor for depression. Reducing the fear of COVID-19, anxiety and stress perception and enhancing perceived social support are beneficial to reduce the level of depression.