Kawasaki disease (KD) is an acute, selflimited vasculitis that predominantly affects mediumsized arteries, particularly the coronary arteries. Recent studies have indicated that microRNAs are involved in many diseases, including KD. However, the detailed mechanism remains unclear. The aim of the present study was to explore the role of miR186 in KD and potentially discover a new target for KD treatment. The results demonstrated that miR186 was upregulated in serum from patients with KD and KD serum could increase miR186 transcript levels in endothelial cells (HUVECs). Overexpression of miR186 mimic induced HUVEC apoptosis through mitogenactivated protein kinase (MAPK) activation by targeting and inhibiting SMAD family member 6 (SMAD6). Furthermore, KD serum induced HUVEC apoptosis through miR186. In conclusion, the present results suggested that KD serumassociated miR186 has an essential role in endothelial cell apoptosis by activating the MAPK pathway through targeting the SMAD6 gene.