The mental health problems have been increasingly threatening the development of adolescence in China, it is very necessary to explore the protective factors preventing adolescents' negative mental health. Previous studies suggested that growth mindset benefits mental health. However, the internal psychological mechanism underlying this relationship is still unclear. This study investigated the relation between growth mindset and negative mental health among Chinese adolescence, and simultaneously tested the mediating effect of psychological resilience and the moderating role of gender in the mediation process of this relation. A total of 1204 middle school students (624 male students and 580 female students) in China completed measures on growth mindset, psychological resilience, and negative mental health. The results revealed that growth mindset not only directly predicted negative mental health, but also indirectly predicted negative mental health through the mediating path of psychological resilience. Moreover, the mediating effect of psychological resilience in the relationship between growth mindset and negative mental health was moderated for females and not males. These findings indicated that intervention focus on growth mindset could improve psychological resilience and prevent negative mental health among middle school students.