Abstract: Objective：To investigate of special AT-rich sequence-binding protein 2（SATB2） in oral squamous cell carcinoma （OSCC）tissue samples，and then to study the proliferation roles of SATB2 in OSCC cells. Methods：The of SATB2 in OSCC and HN4 cell lines are tested by Western blot and qRT-PCR, cellular immunofluorescence was performed to further characterize the subcellular distribution of SATB2 in HN4 cell lines． Using lentivirus overexpressed SATB2, in vitro, cell proliferation were assessed by CCK-8 experiments and the cell cycles were measured by flow cytometry, the protein change of cell cycle-related protein P63, Cyclin B1 and STAT3 phosphorylation were tasted by Western blot. In vivo, the growth of tumor transplation with HN4 cells and Lv-SATB2-HN4 cells in nude mice was further observed . Results：The of SATB2 in OSCC and HN4 cell lines are tested by Western blot and qRT-PCR, and of SATB2 in OSCC tissues is higher than para-carcinoma tissues and of SATB2 in HN4 cells is higher than the oral keratin forms cells （P＜0.05）. CCK-8 assay, flow cytometry and xenograft model showed that over SATB2 in HN4 cell lines significantly promoted cell proliferation, cell cycle-related protein P63，Cyclin B1 had been significantly up-regulated and STAT3 phosphorylation obviously enhanced．Conclusions：SATB2 was highly expressed both in OSCC tissues and HN4 cell lines. Either in vitro or in vivo , over of SATB2 promoted cell proliferation.