Oral squamous cell carcinoma (OSCC) constitutes over 90% of all cancers in the oral cavity. The prognosis for patients with invasive OSCC is poor; therefore， it is important to understand the molecular mechanisms of invasion and subsequent metastasis not only to prevent cancer progression but also to detect new therapeutic targets against OSCC. Recently， extracellular vesicles-particularly exosomes-have been recognized as intercellular communicators in the tumor microenvironment. As exosomic cargo， deregulated microRNAs (miRNAs) can shape the surrounding microenvironment in a cancer-dependent manner. Previous studies have shown inconsistent results regarding miR-200c-3p expression levels in OSCC cell lines， tissues， or serum-likely because of the heterogeneous characters of the specimen materials. For this reason， single-cell clone analyses are necessary to effectively assess the role of exosome-derived miRNAs on cells within the tumor microenvironment. The present study utilized integrated microarray profiling to compare exosome-derived miRNA and exosome-treated cell-derived mRNA expression. Data were acquired from noninvasive SQUU-A and highly invasive SQUU-B tongue cancer cell clones derived from a single patient to determine candidate miRNAs that promote OSCC invasion. Matrigel invasion assays confirmed that hsa-miR-200c-3p was a key pro-invasion factor among six miRNA candidates. Consistently， silencing of the miR-200c-3p targets， CHD9 and WRN， significantly accelerated the invasive potential of SQUU-A cells. Thus， our data indicate that miR-200c-3p in exosomes derived from a highly invasive OSCC line can induce a similar phenotype in non-invasive counterparts.