The aim of this study was to investigate the association between orthodontic treatment need and oral health‐related quality of life (OHRQoL) among 12‐yr‐old children. The study also assessed whether self‐esteem modifies and/or moderates this relationship. Cross‐sectional data on 406 schoolchildren aged 12 yr were analyzed. Data on socio‐economic and demographic characteristics, dental pain, self‐esteem, and OHRQoL were collected using validated questionnaires. Orthodontic treatment need was assessed, through dental examinations, using the dental aesthetic index (DAI). Multiple negative binomial regression and path analysis were used to estimate the association of orthodontic treatment need and self‐esteem with OHRQoL. A modifying effect of self‐esteem on the relationship between DAI and OHRQoL was observed. Self‐esteem did not mediate the abovementioned relationship. Children with lower scores of self‐esteem had worse OHRQoL among those with lower orthodontic treatment need (a DAI score of < 31). However, self‐esteem did not influence the association between DAI and OHRQoL in children with greater orthodontic treatment need (a DAI score of ≥ 31). Self‐esteem attenuated the impact of malocclusion on OHRQoL in children with minor or definite malocclusion, but not among those with severe or very severe malocclusion. Self‐esteem appears to buffer the impact of malocclusion on OHRQoL in children with minor orthodontic treatment need.