Oral　squamous　cell　carcinomas　(OSCC)　is　the　most　common　head　and　neck　cancer　worldwide,　with　more　than　300,000　new　cases　being　diagnosed　annually.　Studies　have　shown　that　miRNAs　are　involved　in　the　process　of　growth,　differentiation,　apoptosis,　invasion　and　metastasis　of　OSCC　tumor　cells.　How　miRNAs　work　together　to　contribute　to　this　process　is　still　largely　unknown.　The　goal　of　our　study　was　to　characterize　the　co-expression　network　of　miRNAs　and　to　identify　the　miRNA　subnetworks　(modules)　that　were　significantly　associated　with　the　OSCC　cancer　status.　We　also　searched　hub　miRNAs　that　might　play　a　vital　role　in　the　development　of　OSCC.　We　applied　the　weighted　gene　co-expression　network　analysis　(WGCNA)　to　the　miRNA　expression　profile　data　from　a　paired　design　study　contributed　by　Shiah　et　al.　To　account　for　the　within-pair　correlation,　a　linear　mixed　model　(LMM)　was　constructed　to　test　the　associations　of　miRNA　modules　to　cancer　status.　Two　significant　modules　(turquoise　module　with　254　miRNAs　and　grey　module　with　309　miRNAs)　were　identified.　The　miRNA　miR-let-7c　was　the　hub　miRNA　in　the　turquoise　module　in　terms　of　node　degree.　Finally,　we　used　miRsystem　to　perform　the　target　gene　prediction　and　KEGG　pathway　enrichment　analysis　of　miRNAs　within　the　two　modules.　Interestingly,　the　two　modules　have　similar　sets　of　target　genes　so　that　the　top　6　enriched　KEGG　pathways　for　the　2　modules　were　the　same.　Compared　with　the　probe-wise　test　used　by　Shiah　et　al.,　we　took　the　network　approach　and　identified　significant　OSCC-associated　miRNA　modules,　which　could　help　uncover　the　mechanism　that　miRNAs　interplay　each　other　to　contribute　to　OSCC.