Based on the ecological systems theory, this study explored the influence factors of mental health of high school students.A sample of 1020 high school students from Sichuan Province completed a questionnaires survey. The results showed that: 1) Family cohesion could predict mental health negatively. 2) Meaning in life mediated the relationship between family cohesion and mental health problems. 3) Social support significantly regulated the first and second half paths of mediating effect. With the improvement of social support, the positive predictive effect of family cohesion on meaning in life and the negative predictive effect of meaning in life on mental health problems were significantly enhanced.