Objective: To describe the prevalence and relationship between moderate to vigorous physical activity(MVPA), screen time (ST) and depressive symptoms among middle school students in Guangzhou, and to provide a reference for adolescent depression prevention and control. Methods: Using stratified cluster random sampling method, a total of 2 140 students were selected from one urban area and one suburban country for MVPA, ST and depressive symptoms investigation. Logistic regression was used to analyze relations among MVPA, ST and their combined patterns for depressive symptoms. Results: A total of 89.72% students failed to meet the MVPA recommendations, girls (95.52%) were higher than boys(84.38%). Totally 67.38% of the students failed to meet the ST recommendations, boys (69.75%) were higher than girls(64.81%). The prevalence of depressive symptoms was 27.01%, girls (31.58%) higher than boys(22.80%). MVPA, ST failure compliance rate and depression symptoms detection rate of vocational high school and ordinary high school were higher than junior high school ( χ 2=6.40,121.71,27.37, P ＜ 0.05 ). Logistic regression analysis showed that the OR for depressive symptoms was 1.19 ( P =0.35) in students whose MVPA time achieving 1 h<7 d in the last week, and was 1.93 ( P <0.01) in students with the ST>2 h/d independently, no significant interactions were observed. Students with both MVPA time 1 h<7 d in the last week and the ST>2 h/d were more likely to report depressive symptoms( OR=2.03, P <0.05). Conclusion Insufficient MVPA, prolonged ST and high prevalence of depressive symptoms are observed among middle school students in Guangzhou. Students with both insufficient MVPA and prolonged ST are more likely to suffer from depressive symptoms. Specific psychological care and health education regarding physical activity and screen behavior should be implemented to students with different characteristics, as well as their parents for depressive symptom prevention.