The interest in the psychological aspects of orthodontic treatment increases, but a drawback of many studies is that the psychological characteristics of the children themselves are often ignored. One of these psychological attributes is self-esteem (SE), which is a relatively stable personal resource that might moderate the effects of conditions or events. The aim of this study was to investigate whether there is a relationship between orthodontic treatment need and oral health-related quality of life (OHRQoL) and whether this relationship is influenced by SE. This cross-sectional study comprised 223 children (113 boys and 110 girls) between 11 and 16 years of age (mean age 13.2 years), seeking orthodontic treatment. The OHRQoL was scored by the use of the Child Perception Questionnaire (CPQ(11-14)). The Dutch adaptation of the Harter's Self-Perception Profile was used to assess SE, and the Index of Orthodontic Treatment Need defined the need for treatment. Spearman correlations, Mann-Whitney U-tests, and regression models were used to analyze the data. There was a significant relationship between orthodontic treatment need and OHRQoL, and between SE and OHRQoL. No evidence was found that SE moderates the relationship between OHRQoL and treatment need.