OBJECTIVE To assess the oral health-related quality of life (OHRQoL) of preschool children with cleft lip and palate (CLP) and their relatives. METHODS In this cross-sectional study, 55 2-5-year-old children with the history of CLP were randomly selected from those referred to Shiraz Lip and Palate Cleft Research Center and treated with single-stage closure (Push back palatoplasty). Furthermore, same number of children with the same age who attended the Shiraz School of Dentistry for routine dental care were selected as control group using randomized sampling. Children's demographic data were obtained from their parents. Farsi version of the Early Childhood Oral Health Impact Scale (F-ECOHIS) was used for evaluating these children's QoL. RESULTS We found a significant difference in OHRQoL between children with CLP and children without CLP in the overall score of F-ECOHIS and all of subscales. In the impact on children subscale, the difference between these groups was remarkable in limitations' domain. As for difficulties faced by children, question on "difficulty in pronouncing words" had the highest average score. Furthermore, in impact on family, in parental distress domain, the difference between these groups was remarkable. For difficulties faced by family, financial impact got the highest average score. No significant difference was found between boys and girls with CLP in all subscales. While according to the score of total F-ECOHIS in unilateral and bilateral CLP children, there was statistically significant difference in these groups. CONCLUSIONS Since oral clefts affect the QoL of children and their families even after the usual treatments, the implementation and maintenance of multidisciplinary interventional strategies are required for establishment of facial esthetics, oral function, and psychological support for such individuals.