Abstract: Objective：To investigate expression of miR-34a in oral squamous cell carcinoma (OSCC) tissue samples, and then to study whether it can inhibit the proliferation, migration and invasion of oral squamous cell carcinoma by down-regulating the expression of SATB2. Methods：The expression of miR-34a in OSCC, HN6 cell line was tested by qRT-PCR．We used lentivirus to overexpress SATB2 and constructed miR-34a mimic plasmid, in vitro. Cell proliferation was assessed by CCK-8 experiments and the cell cycles were measured by flow cytometry. Cell migration ability was measured by cell wound healing test and transwell test. Cell invasion ability was measured by trans invasion test and the protein change of cell invasion-related protein MMP-2 and MMP-9 were tested by Western blot. In vivo, the growth of tumor in nude mice was further observed to examine whether miR-34a can affect the growth of transplanted tumors in vivo by modulating the expression of SATB2. Results：The expression of miR-34a in OSCC tissues and cell line are lower than para-carcinoma tissues and oral keratin forms cells (P＜0.05). After transfecting miR-34a mimic plasmid, the ability of proliferation, metastasis and invasion of Lv-SATB2-HN6 was significantly reduced. Co-transfection of the miR-34a mimics specifically decreased the expression of the SATB2. Conclusions：MiR-34a can down-regulate SATB2 to inhibit the proliferation, migration and invasion of OSCC.