Background As a new drug for the treatment of infantile hemangioma, the efficacy of propranolol has been confirmed by numerous case reports and is rapidly becoming a first-line drug for the clinical treatment of infantile hemangioma. This randomized controlled study demonstrated that propranolol is effective in the treatment of infantile hemangiomas and is well tolerated by children. Abstract Objective Propranolol is a safe and effective drug for the treatment of infantile hemangiomas (IHs), resulting in a lighter color and smaller size of the tumor. Methods Forty children aged 9 to 5 years with facial hemangiomas or potentially disfiguring hemangiomas were randomly divided into a propranolol group and a placebo group. The propranolol group was given propranolol 2 mg/kg.d orally three times a day for 6 months, while the children in the placebo group were given the same dose of placebo in the same manner of administration. Pre-treatment investigations included electrocardiogram, echocardiogram and relevant laboratory tests. Follow-up monitoring indicators included heart rate, blood pressure, and blood glucose. Children younger than 6 months of age were admitted for monitoring at the end of the first and second weeks of initial trial dose therapy. Tumor volumes were measured at weeks 0, 4, 8, 12, 16, 20, and 24 by blinded method, and tumor photographs were evaluated and scored at weeks 0, 12, and 24. Results The growth of hemangiomas in the propranolol group stopped at week 4 of treatment. There was a significant difference in the rate of change in tumor volume between the two groups, with the most significant difference at 12 weeks of treatment. At the 12th and 24th weeks of treatment, the tumor color of the children in the propranolol group was significantly less than that of the control group, with significant shrinkage (P=0.01 versus P=0.001). One patient withdrew from the trial due to respiratory infection, and other complications included bronchitis, gastroenteritis, streptococcal infection, chills in the extremities, dental caries, and sleep disturbances. Conclusion Oral propranolol hydrochloride 2 mg/kg.d treatment of focal and segmental IHs in infants aged <6 months and children younger than 5 years resulted in tumor shrinkage and color fading with positive efficacy.