Background Molar incisor hypomineralization (MIH) is associated with unfavourable dental conditions such as dental caries and may consequently impact oral health‐related quality of life (OHRQoL). Objective To assess the impact of MIH on OHRQoL in children with early mixed dentition. Method A population‐based cross‐sectional study of 728 8‐year‐old children from the public school system in Curitiba, Brazil, was conducted. The Child Perception Questionnaire for 8‐ to 10‐year‐olds (CPQ8‐10) was used to evaluate OHRQoL. MIH was diagnosed according to the European Academy of Paediatric Dentistry (EAPD) criteria. The assessments of MIH, dental caries, and malocclusion were performed by four calibrated examiners (κ ≥ 0.80). Demographic and socioeconomic data (DSE) were obtained from the children's parents/caregivers using a structured questionnaire. The analysis of OHRQoL determinants was performed through a three‐level hierarchical approach: mesial (DSE), intermediate (clinical conditions), and distal (child's oral self‐perception), using Poisson regression with robust variance (α = 0.05). Results The prevalence of MIH was 12.1% (95% CI: 10‐15). An association was found between MIH and OHRQoL in the “oral symptoms” domain of the CPQ8‐10 (PR: 1.07, 95% CI: 1.03‐1.11, P < 0.001) after adjusting for other clinical variables and DSE. Conclusion Molar incisor hypomineralization was associated with a greater impact on OHRQoL in children's oral symptoms.