• MiR-206 downregulated in proliferative hemangioma suppressed HemEC malignancy via modulating ECM-related genes.• In vitro and in vivo research showed that miR-206 increases ECM accumulation by targeting DNMT3A, preventing HemEC malignancy and alleviating IH.• Overexpression of DNMT3A prevented miR-206 mimic from inhibiting HemECs and regulating ECM. Here, DNMT3A is linked to isolated hemihyperplasia.