Social stigma has been identified as a major concern in healthcare. Its association with quality of life among migrants is rarely assessed. Using data collected through a cross-sectional survey among 1,006 rural-to-urban migrants and 1,020 rural residents in China, this study examines the experience of stigmatization in relation to four domains of quality of life. Rural-to-urban migrants perceived a higher level of social stigma and a lower level of quality of life than their rural counterparts. Multiple regressions indicated the importance of social stigma in accounting for subjective quality of life for migrants. In addition, personal income, family economic status and health status were positively associated with increased quality of life. Social stigma has a significant influence on quality of life among rural-to-urban migrants in China. Future interventions should seek to improve public attitudes to rural-to-urban migrants and generate action to eliminate stigma, discrimination and prejudice.