Kawasaki disease (KD) has complexly clinical features and laboratory parameters and there is no definitive biomarker for this disease and the therapy of KD also is complex and uncertain. In this study, 102 KD patients and 80 healthy controls were enrolled in this study and the serum microRNAs were detected by qRT-PCR. The results showed that, compared with KD patients with a good response to high-dose intravenous immunoglobulin (IVIG) therapy, serum miR-200c and miR-371-5p were significantly higher in KD patients with no response to IVIG therapy; compared with KD patients not needing plasma exchange, these two microRNAs were also significantly higher in KD patients needing plasma exchange. In addition, combination of serum miR-200c and miR-371-5p reflected obvious separation between KD patients and healthy controls or between KD patients with no response to IVIG therapy and KD patients with good response to IVIG therapy or KD patients needing plasma exchange and KD patients not needing plasma exchange. Finally, both serum miR-200c and miR-371-5p were also significantly lower in KD under different kinds of therapy. Therefore, serum miR-200c and miR-371-5p have ability as the useful diagnostic biomarkers and therapeutic targets in Kawasaki disease.