Purpose To explore the health-related quality of life (HRQoL) and associated variables in children with chronic myeloid leukemia in the chronic phase (CML-CP) receiving tyrosine kinase inhibitors (TKIs).Methods A cross-sectional questionnaire was given to children with CML and their parents, who were <18 years at diagnosis of CML and <19 years at study. The questionnaire consisted of three parts, including demographic information, clinical information, and the Chinese version of Pediatric Quality of Life InventoryTM (PedsQL™) Cancer Module 3.0 as HRQoL questionnaire.Results 289 questionnaires were collected, and data from 207 (71.6%) respondents were analyzed. Multivariate analysis showed that children with symptoms had worse pain (-10.7; P<0.001), nausea(-17.9; P<0.001), treatment anxiety(-6.7; P=0.008), worse appearance self-assessment (-7.5; P<0.001) and communication problems(-3.9; P=0.028), and worse HRQoL(-4.1; P=0.013). Children whose mothers had low educational qualifications complained worse pain(-8.3; P=0.005), worried more about the future (-11.6; P=0.002), had poor self-assessment (-5.1; P=0.045), and worse HRQoL (-6.5; P=0.002). Children at a younger age of study when studied had more procedural anxiety (3.3; P=0.008), more cognition problems (3.4; P=0.001), and worse HRQoL (1.4; P=0.040), while increasing age at diagnosis had worse appearance self-assessment (-2.1; P=0.015) and HRQoL (-1.4; P=0.039). Other variables significantly associated with worse HRQoL included female sex and rural household registration. Parents reported more gastrointestinal disorders and worry about the future and had less concern about appearance than reported children.Conclusions This study suggests that female gender, increasing age at diagnosis, younger age at study, lower mother’s education level, and TKI-related symptoms reported were significantly-associated with worse HRQoL. Parents and children have different priorities in the HRQoL.