Interleukin-10 (IL-10) is the key regulator of immune responses preventing the undesirable exaggerated ones. Genetic variation in the promoter region of IL-10 may influence its serum level and contribute to susceptibility to bronchial asthma in children. This is a case–control study including 100 patients and 100 healthy control children who had undergone skin prick test, estimation of total IgE and serum level of IL-10 by enzyme-linked immunosorbent assay, and polymerase chain reaction-restriction fragment length polymorphism for IL-10 gene polymorphism. A significant association between IL-10 polymorphism and susceptibility to pediatric asthma was found. AA genotype represented 66% of the patient group compared to only 6% of the control group, while the AG genotype was detected in 20% of patients and 4% of controls. In contrast, wild genotype GG was found in 14% of patients and 90% of controls, with a highly statistically significant difference between both groups (P < 0.001). The serum level of IL-10 was significantly elevated in the GG genotype in comparison to other genotypes (P < 0.001), and it was negatively correlated with the severity of asthma among the studied pediatric asthmatic group (P < 0.001). In conclusion, IL-10 polymorphism may play an important role in the development of bronchial asthma in children.