Introduction: Caregivers are crucial providers of lifelong care for mentally retarded children due to their specific disability, and their rehabilitation training and living standards are closely related to caregivers’ quality of life. Therefore, this study selected S District of Chongqing to conduct a cross-sectional study on the quality of life of caregivers of mentally retarded children. Methodology: The study was conducted at three specialized rehabilitation centers in Chongqing, China, using Basic Information Questionnaire and Generic Quality of Life Inventory-74 for caregivers of mentally retarded children, and the study sample included 112 caregivers of mentally retarded children and 104 normal children’s caregivers. Results: The caregivers of mentally retarded children have higher scores than those of normal children. There are significant differences among them in the quality of life and in material condition caused by family annual income, in material condition caused by home address, in social function caused by father’s occupation, and in material condition and in psychological function caused by father’s education level. Conclusion: The caregivers of mentally retarded children have lower quality of life than those of normal children. Some demographic variables like the annual family income, home address, father’s occupation and father’s education level have effects on caregivers’ quality of life.