To explore the multiple linear regression model, the author puts forward research on the influencing factors of college students’ mental health literacy. The author selected the Mental Health Guidance Center of A University to investigate the mental health status of 5806 students in 2010, according to the questionnaire data, the factors affecting mental health were verified. The influence of various factors on mental health is clarified by establishing a multiple linear regression model, the statistical data and the calculation results of the model are used to more accurately explain the impact of various factors on mental health, to facilitate targeted mental health education. The results of multiple linear regression analysis showed that gender, family history of mental illness, self-stigma, and public stigma were the influencing factors of college students’ mental health literacy. The mental health literacy of college students is at a medium level, which is affected by many factors, therefore, targeted measures should be taken according to the influencing factors to improve the mental health of college students.