MicroRNAs (miRNAs) negatively regulate the expression of target genes at the post-transcriptional level in diverse biological processes. We have previously identified a group of novel miRNAs in proximal nerve following rat sciatic nerve transection by Solexa sequencing. In this study, the biological function and action mode of miR-sc8, one of the above identified miRNAs, were investigated. An increased expression of miR-sc8 inhibited cell proliferation and migration of Schwann cells (SCs), and inversely, silencing of the miR-sc8 expression promoted cell proliferation and migration of SCs. The epidermal growth factor receptor (Egfr) was identified as the target gene of miR-sc8, which exerted negative regulation of Egfr by translational suppression. The temporal change profile of the miR-sc8 expression was negatively correlated with that of the Egfr expression in proximal nerve following sciatic nerve transection. Moreover, Knockdown of Egfr attenuated the promoting effects of miR-sc8 inhibitor on SC proliferation and migration. Overall, our data indicate that miR-sc8 affects phenotype modulation of SCs by targeting Egfr, providing further insights into the regulatory role of miRNAs in peripheral nerve regeneration.