Objective To screen and analyze the serum microRNA (miRNA) profile of moyamoya disease (MMD), so as to elucidate the possible pathogenesis of the disease. Methods MiRNA microarray was used to test the serum of 10 MMD patients and 10 healthy controls to identify the miRNA profile. Some angiogenesis-associated miRNAs were validated by RT-PCR. TargetScan software was used for prediction and the differential miRNAs were obtained. Furthermore, the key signal pathways and miRNAs involved in MMD pathogenesis were analyzed by gene ontology and pathway analysis. Results A genome-wide miRNA array revealed 50 up-regulated and 44 down-regulated miRNAs in the sera of MMD patients; several important miRNA families and clusters were detected. RT-PCR assay confirmed that miRNA-106b, miRNA-130a and miRNA-126 were significantly up-regulated and miRNA-125a-3p was significantly down-regulated in the serum of MMD patients, suggesting the high reliability of miRNA array. Pathway analysis showed that the most enriched pathway was mTOR signaling pathway, with 16 potential functional targets. Conclusion We have identified the serum miRNA signature in MMD patients, and further analysis indicates that mTOR pathway-associated miRNAs might play an important role in MMD pathogenesis.