BackgroundDepression is one of the most common types of mental disorders. Guided by the theory of social determinants of health (SDH), the study aimed to assess the prevalence of depressive symptoms and to identify factors related to depressive symptoms in the general population of China. MethodsA cross-sectional, online survey was conducted among 101,392 residents from 31 provinces of mainland China from January to March 2019, and 97,126 survey responses were included in the final analysis. Multilevel linear regression models were used to identify SDH associated with depressive symptoms. ResultsThe prevalence of depressive symptoms (PHQ-9 scores ≥10) in Chinese residents was 15.81 %. The results of the multilevel analysis demonstrated that depressive symptoms were affected by various factors on five levels, including individual characteristics, behavioral lifestyle, community support network, social structural factors, and macro social factors. LimitationsThe cross-sectional design of the study makes it difficult to establish causality between variables. ConclusionsThe prevalence of depressive symptoms is high among general population in China. According to the theory of SDH, the study shows that the depressive symptoms are complex and involves all areas of social life. Therefore, adopting a multi-level, cross-sectoral intervention approach will be instrumental to improving the mental health of residents in China.