Poor mental health among nurses not only hinders professional performance but also affects the quality of healthcare provided. To improve the prevention and management of depression among nurses in mainland China, we investigated the association between working conditions and depressive symptoms using a cross-sectional study with a sample of 3474 nurses with more than 1 year of work experience in public hospitals in Shenzhen in southern China. Participants completed a structured questionnaire and a validated measure of depressive symptoms. Multivariable linear mixed models were used to identify work-related risk factors for depressive symptoms scores. An estimated 38% of nurses had depressive symptoms. More than 10% of the nurses often experienced workplace violence, and 64.22% encountered it occasionally. Depressive symptoms were associated with frequent workplace violence, long working hours (more than 45 hours per week), frequent night shifts (two or more per week), and specific departments. These findings indicate that interventions to minimize workload and improve nurse-patient relationships are essential to combat depressive symptoms among nurses. Additionally, in the prevention and management of depression among nurses, we must consider inter-department differences.