OBJECTIVE: To investigate the association between drooling in children with cerebral palsy (CP) and their health-related quality of life (HRQOL), as well as the possible variables that predict their HRQOL. METHOD: A cross-sectional design was used for this study. Children with CP, without other identified disease, aged 2 to 6 years, who drool (n = 33) or did not drool (n = 14), were included. The dependent variables were the physical health summary scores and the psychosocial health summary scores of the Pediatric Quality of Life Inventory version 4.0. The t test, Pearson product-moment correlation, Mann-Whitney U test and stepwise regression analysis were used for statistical analysis. RESULTS: The physical health and psychosocial health summary scores of the children that drooled (16.29 ± 15.97 and 42.92 ± 17.57, respectively) were lower than for the children that did not drool (31.97 ± 22.22 and 57.09 ± 12.21, respectively; P < 0.01). The drooling ranking score was negatively correlated with the physical health summary score (r = -0.355; P < 0.05) and the psychosocial health summary score (r = -0.381; P < 0.01). The stepwise regression showed that gross motor development and the drooling ranking score predicted 56.6% of the variability of the physical health summary score (R(2) = 0.566; P < 0.01). The language development score predicted 25.6% of the variability of the psychosocial health summary score (R(2) = 0.256; P < 0.01). CONCLUSION: Drooling was associated with a lower HRQOL. Prediction of the physical health summary score was more closely associated with gross motor development and the drooling ranking scores. Prediction of the psychosocial health summary score was more closely associated with the language development of children with CP aged 2 to 6 years.