Objective   To explore the relationship among preschool education female students' negative affect, self-efficacy, self-esteem, and life satisfaction, and assess the mediating role of self-efficacy and self-esteem between negative affect and life satisfaction. Methods   A total of 382 preschool education female students in higher vocational college were investigated by the depression anxiety stress scale 21(DASS-21), general self-efficacy scale(GSES), self-esteem scale(SES), and satisfaction with life scale(SWLS). Results   ① Pearson correlation analysis showed that negative affect, self-efficacy, self-esteem, and life satisfaction correlated significantly with each other; negative affect were negatively correlated with self-efficacy, self-esteem, and life satisfaction; and self-efficacy, self-esteem, and life satisfaction scores were positively correlated with each other. ② Negative affect influenced life satisfaction directly and indirectly through three indirect paths: self-efficacy, self-esteem, and self-efficacy-self-esteem. ③ Self-efficacy and self-esteem played a chain mediating role between negative affect and life satisfaction, and the total mediating effect accounted for 44.24% of the total variance. Conclusion   Negative affect and life satisfaction of preschool education female students are influenced by self-efficacy, self-esteem, or through the mediating chains of self-efficacy and self-esteem.