The purposes of this study were to investigate the mediating effect of smartphone addiction and depression on neuroticism and quality of life. Self-reported measures of neuroticism, smart-phone addiction, depression, and quality of life were administered to 722 Chinese university students. Results showed smartphone addiction and depression were both significantly affected neuroticism and quality of life. The direct effect of neuroticism on quality of life was significant, and the chain-mediating effect of smartphone addiction and depression was also significant. In conclusion, neuroticism, smartphone addiction, and depression are important variables that worsen quality of life.