Purpose: To assess whether different levels of malocclusion have different effects on the oral health-related quality of life (OHRQoL) and which domains of OHRQoL could be affected. Materials and Methods: Nine electronic databases were searched. To make studies comparable, studies using the Child Perceptions Questionnaire (CPQ) to measure OHRQoL, and the Dental Aesthetic Index, Index of Orthodontic Treatment Need, and Index of Complexity, Outcome and Need to measure malocclusion were selected for systematic review. Meta-analysis was performed to calculate the weighted mean scores of CPQ. The two independent samples t-test was used to detect whether different severity groups of malocclusion have different CPQ scores. Results: A total of 22 studies were included in this review and 6 were included in the meta-analysis. Most studies used a cross-sectional design and convenience sampling. Meta-analysis showed that the weighted mean scores of CPQ increased with malocclusion severity. The t-test showed nearly all levels of malocclusion affected the domains of functional limitation and social well-being; only very severe malocclusion affected the domains of oral symptoms, emotional well-being and the overall OHRQoL (p 0.05). Conclusion: When OHRQoL was assessed by CPQ11-14 and malocclusion was assessed by orthodontic indices, children with malocclusion could have oral functional limitations and worse social lives; children with very severe malocclusion could further develop oral symptoms and had worse emotional experiences. Future longitudinal population-based studies would be helpful to confirm these results. Keywords: malocclusion severity, quality of life, child perceptions questionnaire, systematic review