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Objectives: To explore the relationship between health-related quality of life (HRQOL) status and associated factors among rural-to-urban migrants in China. Methods: A cross-sectional survey was conducted with 856 rural-to-urban migrants working at small- and medium-size enterprises (SMEs) in Shenzhen and Zhongshan City in 2012. Andersen's behavioral model was used as a theoretical framework to exam the relationships among factors affecting HRQOL. Analysis was performed using structural equation modeling (SEM). Results: Workers with statutory working hours, higher wages and less migrant experience had higher HRQOL scores. Need (contracting a disease in the past two weeks and perception of needing health service) had the greatest total effect on HRQOL (β = −0.78), followed by enabling (labor contract, insurance purchase, income, physical examination during work and training) (β = 0.40), predisposing (age, family separation, education) (β = 0.22) and health practices and use of health service (physical exercise weekly, health check-up and use of protective equipments) (β = −0.20). Conclusions: Priority should be given to satisfy the needs of migrant workers, and improve the enabling resources. [ABSTRACT FROM AUTHOR]