<p>Schwannomas are the most prevalent benign tumors in peripheral nerve. Gene expression alterations are key factors in the formation of schwannomas. MiRNAs, as desirable biomarkers, are usually used for diagnosis or treatment of tumors. The aim of this study is to investigate the diagnostic value of tissue-derived differentially expressed miRNAs in schwannoma serum samples and evaluated target genes involvement in biological pathways. In silico analysis of microarray datasets was used to evaluate the differential expression of miRNAs and mRNAs. MiRNA target genes were predicted using StarBase tools. For further exploration, DAVID tools were used to investigate Gene Ontology of Biological Process, Cellular Components and Molecular Functions of target genes. Lastly, RT-qPCR was performed to determine miRNA expression levels in serum samples from 20 patients and 20 healthy individuals. Bioinformatics results identified 149 miRNAs with differential expression and among them seven miRNAs selected for further study. In addition microarray data analysis identified 2475 differentially expressed mRNAs, of which 761 were located in miRNA target genes. Functional enrichment analysis showed that these target genes were involved in schwannoma related pathways such as P53 and VEGF. Our experimental results demonstrated that among candidate miRNAs, miR-145, miR-34a and miR-222 were downregulated in the vestibular schwannoma patients compared with normal subjects and they could distinguish schwannoma samples from normal ones with AUC &gt; 70%. In this study, we report for the first time three serum miRNAs in schwannoma patients, which may not act as exclusive biomarkers but represent a potentially valuable component of a circulating diagnostic panel.</p> Graphical Abstract <p></p>