Objective Exposure to the coronavirus disease 2019 (COVID-19) was associated with high risk of mental health problems among frontline nurses. This study examined the prevalence of depressive symptoms (depression hereafter) and its impact on quality of life (QOL) in otorhinolaryngology (ENT) nurses during the COVID-19 pandemic in China. Methods An online study was conducted between March 15 and March 20, 2020. Depression and QOL were assessed using standardized instruments. Results A total of 1,757 participants were recruited. The prevalence of depression was 33.75% (95% CI: 31.59%-35.97%). Results emerging from multiple logistic regression analysis showed that direct care of COVID-19 patients (OR: 1.441, 95% CI: 1.031–2.013, P = 0.032), and current smoking (OR: 2.880, 95% CI: 1.018–8.979, P = 0.048) were significantly associated with depression. After controlling for covariates, ENT nurses with depression had a lower overall QOL compared to those without depression (F(1, 1757)= 536.80, P < 0.001). Conclusions Depression was common among ENT nurses during the COVID-19 pandemic in China. Considering the negative impact of depression on QOL and care quality, regular screening for depression should be conducted in ENT nurses and treatment should be provided.