BackgroundPropranolol is the first-choice treatment for severe infantile hemangioma (IH). However, 10- 30% of lesions relapse after propranolol treatment. The mechanisms underlying IH recurrence after propranolol treatment have not been completely elucidated.MethodsThis study combined an examination of hemodynamic changes with research regarding hemangioma stem cells (hscs) with differentially expressed microRNAs (miRNAs) to identify the factors affecting IH recurrence after propranolol treatment. Hemodynamic changes were monitored in 21 recurrent cases using high-frequency color Doppler ultrasound, and hscs were treated with different concentrations of propranolol. The levels of differentially expressed miRNAs and the activity of related pathways were then compared between 18 recurrent and 20 non-recurrent IH cases.ResultsDuring treatment, lesion depth and vessel density decreased, and the lesion resistance index increased. Obvious lesions and vessel signals were observed in recurrent cases compared with non-recurrent cases. Propranolol effectively inhibited hscs proliferation. Twenty-two differentially expressed miRNAs were found in the recurrent group compared with the non-recurrent group.ConclusionRecurrence may be attributed to a combination of events. Serum biomarkers and drug treatments for IH recurrence must be studied further.