Background: Mental health problems are common among clinicians working in public hospitals even in the late stage of the COVID-19 pandemic. Network analysis is a novel approach to explore interactions between mental health problems at the symptom level. This study examined the network structure of comorbid depression and anxiety and their associations with quality of life (QOL) among hospital clinicians in China during the late stage of the COVID-19 pandemic. Methods: A total of 4931 participants were recruited from October 13 to 22, 2020. The nine-item Patient Health Questionnaire (PHQ-9), seven-item Generalized Anxiety Disorder Scale (GAD-7), and the World Health Organization Quality of Life Questionnaire-Brief Version (WHOQOL-BREF) were used to measure depressive and anxiety symptoms, and QOL, respectively. Central and bridge symptoms were identified with centrality and bridge centrality indices, respectively. Network stability was examined using the case-dropping procedure. Results: The prevalence of depression (defined as PHQ-9 total score ≥ 5) was 35.1 % [95 % confidence interval (CI) = 33.73–36.41 %)], the prevalence of anxiety (GAD-7 total score ≥ 5) was 32.5 % (95 % CI = 31.20–33.84 %), while the prevalence of comorbid depression and anxiety was 26.9 % (95 % CI = 25.7–28.2 %). “Impaired motor skills”, “Trouble relaxing” and “Uncontrollable worry” were the central symptoms in the whole depression-anxiety network. “Irritability”, “Feeling afraid” and “Sad mood” were the most key bridge symptoms linking depression and anxiety. Three symptoms (“Fatigue”, “Trouble relaxing” and “Nervousness”) were the most strongly and negatively associated with QOL. Neither gender nor the experiences of caring for COVID-19 patients was associated with network global strength, distribution of edge weights or individual edge weights. Limitations: The causality between variables could not be established. Depressive and anxiety symptoms were assessed by self-report measures, which may result in recall bias and limitations in capturing clinical phenomena. Conclusions: Both the central (i.e., “Impaired motor skills”, “Trouble relaxing” and “Uncontrollable worry”) and bridge symptoms (i.e., “Irritability”, “Feeling afraid” and “Sad mood”) identified in this network analysis should be targeted in specific treatment and preventive measures for comorbid depressive and anxiety symptoms among clinicians in the late stage of the pandemic. Furthermore, “Fatigue”, “Trouble relaxing” and “Nervousness” are key symptoms to address to improve clinicians' QOL.