ABSTRACT: Background:The body of literature regarding the associations between physical activity and psychological problems lacks consensus. Moreover, the role of gender has been scarcely investigated. The present study sought to fill the gap in the data by examining the associations, if any, between moderate-to-vigorous physical activity (MVPA), psychological problems, and self-harm behaviors based on different biological genders (male-female). Methods:A self-administered questionnaire was used to measure MVPA and multiple psychological problems, including depression and anxiety; general emotion, behavior, and social problems; Attention Deficit Hyperactivity Disorder (ADHD); Oppositional Defiant Disorder (ODD); conduct problems; and self-harm behaviors. Participants were a nationally representative sample of Chinese high school students (N = 13, 349). A multiple logistic regression analysis of MVPA, stratified by gender, was conducted on the risk of psychological problems and self-harm behaviors in the total sample. Results:For boys, a high frequency of MVPA was associated with a lower risk of depression (OR = 0.68, 95% CI [0.57-0.81]) and anxiety (OR = 0.71, 95% CI [0.53-0.96]) compared to the reference group. The moderate frequency of MVPA was associated with a lower risk of ADHD (OR = 0.73, 95% CI [0.56-0.94]) compared to the reference group. For girls, both MVPA groups were associated with a lower risk of depression (moderate MVPA: OR = 0.81, 95% CI [0.70-0.94]; high MVPA: OR = 0.67, 95% CI [0.54-0.83]) compared to the reference group. High MVPA was associated with a lower risk of ADHD (OR = 0.58, 95% CI [0.37-0.89]) compared to the reference group. Only moderate frequency of MVPA was associated with a lower risk of ODD (OR = 0.79, 95% CI [0.64-0.97]). Conclusion:MVPA was associated with a lower risk of depression, anxiety, ADHD, and ODD in a gender-specific and MVPA frequency-specific manner. This implies that for specific psychological issues, PA interventions that are modified based on gender and frequency of MVPA may be more effective than PA interventions without these considerations.