Numerous findings have demonstrated that MicroRNAs dysregulation plays a key role in many neoplasms, including oral squamous cell carcinoma (OSCC), yet the potential mechanisms of microRNAs in chemo-resistance remain elusive. Here, we analyzed the miR-132 expression in OSCC tissues and OSCC cell lines, and explored it role and mechanisms on invasion and migration and cisplatin (CDDP)-induced cell death. The clinical tissues of 37 patients with OSCCs and paired normal tissues were collected. The miR-132 expression in OSCC tissues and cell lines were detected by reverse transcription-quantitative polymerase chain reation (RT-qPCR). The repopulation models were established to mimic the biological processes of OSCC. The results showed that miR-132 expression was significantly decreased in the OSCC tissues and CDDP resistant OSCC cell line (CAL-27/CDDP). miR-132 mimic inhibited cell proliferation, invasion, migration and enhanced the pro-apoptotic ability of CDDP. On the contrary, downregulation of miR-132 promoted proliferation, invasion, migration and conferred OSCC cell resistance to CDDP-induced apoptosis . The TGF-β1 expression in OSCC tissues and CAL-27/CDDP cells was significantly higher. miR-132 significantly inhibited the TGF-β1/Smad2/3 signals. TGF-β1 upregulation significantly promoted OSCC cell proliferation and resumed OSCC cell chemo-resistance in the miR-132 overexpressing cells, which is contrary to the function of miR-132. In summary, miR-132 acts as a tumor suppressor and exerts a substantial role in inhibiting the proliferation, invasion, and enhanced the chemosensitivity to CDDP of OSCC via regulating TGF-β1/Smad2/3 signals . These observations indicate that miR-132 may be a suitable therapeutic target for the treatment of OSCC.