Increasing attention has been paid to the role of caregivers' burden in affecting quality of life (QoL) of schizophrenic patients. However, less is known about potential mediation mechanisms underlying this relationship. The current study aimed to explore the sequential mediating effect of expressed emotion and perceived expressed emotion on the relationship between care burden and QoL among people with schizophrenia. 135 Chinese families (one patient and one caregiver) participated in this study. Caregivers reported their care burden and expressed emotion, patients reported their perceived expressed emotion and QoL. The results of the correlation analysis showed that care burden was negatively related to patients' QoL, including physical, psychological, and social relationships domains, with patients' sex, age, educational level, employment status, and medication-taking as covariates. The sequential mediating effects of criticism and perceived criticism between care burden and QoL were not significant. However, the sequential mediating effects of emotional over-involvement and perceived emotional over-involvement (EOI) between care burden and QoL (including physical and psychological domain) were significant. The results indicated that reducing the burden and expressed emotion of caregivers could be helpful to improve schizophrenia patients' QoL.