Objective To explore the quality of life (QoL) and care burden of Noonan syndrome children. Methods The quality of life and care burden of children with Noonan syndrome were investigated by general data questionnaire, pediatric quality of life inventory 4.0 generic core scales (PedsQL 4.0) and caregiver burden inventory (CBI). Results The median age of 96 children (40 boys and 56 girls) with Noonan syndrome was 4.0 (3.0-5.0) years. The total score of PedsQL in children with Noonan syndrome was 49.3(34.24-59.8), which was far lower than the national norm ( 81. 81 ± 12. 03 ), and the difference was statistically significant (P<0.001). The total score of CBI of primary caregiver was 43. 5 ( 29. 5 - 52. 0 ), indicating a moderate burden. The score of life quality was significantly positively correlated with the total burden score of caregivers (r=0.65, P<0.01), and was significantly positively correlated with three dimensions (time-dependent burden, developmental constraint burden and physical burden) (P< 0. 05 ). There were statistically significant differences in PedsQL scores among families in only child, occupations and education levels of caregivers (P<0.05). Multivariate regression analysis suggested that timedependent burden, developmental constraint burden and physical burden contributed 22.0% to the prediction of life quality. Medical and genetic counseling (100%), multidisciplinary team management (93.8%), rehabilitation training (79.2%), and vaccination (58.3%) were the primary needs of Noonan families in their care. Conclusions The life quality of children with Noonan syndrome is severely low and the burden on caregivers is heavy. Early diagnosis, medical genetic counseling and long-term management planning of Noonan syndrome deserve attention.