This was a national survey that determined the prevalence of depressive symptoms (depression thereafter) and its relationship with quality of life (QOL) in frontline clinicians working in psychiatric hospitals in China during the COVID-19 pandemic. Depression and QOL were assessed using the Patient Health Questionnaire nine items (PHQ-9) and the World Health Organization Quality of Life Questionnaire-brief version (WHOQOL-BREF), respectively. Multivariable logistic regression analyses and analysis of covariance were used. A total of 10,516 frontline clinicians participated in this study, of which, 28.52% (n=2,999) met screening criteria for depression. Compared to those without depression, clinicians with depression had a lower quality of life (F (1, 10515) =2874.66, P<0.001). Higher educational level (OR=1.225, P=0.014), if the number of COVID-19 patients in the hospital catchment area surpassed 500 (OR=1.146, P=0.032), having family/friends/colleagues who were infected (OR=1.695, P<0.001), being a current smoker (OR=1.533, P<0.001), and longer working hours (OR=1.020, P=0.022) were independently associated with higher risk of depression. Living with family members (OR=0.786, P<0.001), and being junior clinicians (OR=0.851, P=0.011) were independently associated with lower odds of depression. The results showed that depression was common in frontline psychiatric clinicians during the COVID-19 pandemic. Timely assessment and effective interventions of depression for frontline clinicians in psychiatric hospitals was warranted.