Objective: To understand the current status of health related quality of life among primary and middle school students aged 9 to 15 years old in Henan Province, and to explore its relationship with negative emotions and social support. Methods: Between January and June 2016, 24 primary and middle schools were selected from 6 cities of Henan Province, and 5 867 primary and middle school students were included and completed the Pediatric Quality of Life Inventory Measurement, Stress Anxiety Depression Scale, Perceived Social Support Scale. Hierarchical linear regression analysis was used to examine the moderating effect of social support. Results: The total score of health related quality of life of primary and middle school students in Henan was (81.21±12.49). There were statistically significant differences in the quality of life among primary and middle school students with different gender, study period, family monthly income, subjective parental relationship and parental education ( P <0.05). Negative emotions were negatively correlated with quality of life ( r =-0.51, P <0.01) and social support ( r =-0.30, P <0.01), while social support was positively correlated with quality of life ( r =0.29, P <0.01). Regression analysis showed that negative emotional was negatively associated with quality of life ( β =-0.23, P <0.01), while social support was positively associated with quality of life ( β =0.16, P <0.01). The interaction of negative emotions and social support was negatively associated with quality of life ( β =-0.18, P <0.01). Conclusion Health related quality of life among 9-15 year old primary and middle school students in Henan province is satisfactory. Social support might buffer the negative impact of negative emotions including depression, anxiety and stress on quality of life of primary and secondary school students.