Abstract: Objective： To investigate the of nuclear matrix protein- special AT-rich sequence binding protein 2 (SATB2) in oral squamous cell carcinoma (OSCC) and its effect on the biological behavior of oral squamous cell carcinoma. Methods：58 cases of oral squamous cell carcinoma were collected and the of SATB2 was detected by immunohistochemical staining. The relationship between SATB2 and the pathological parameters and the overall survival rate was analyzed. Then the HN6 cell lines were transfected with lentivirus containing SATB2 and tested through western blot and RT-PCR as well. Wound healing test,migration tests and invasion tests were preformed for further study of biological roles of SATB2 in HN6 cell lines. Results：The high of SATB2 was not associated with age, sex and pathological grade, but was closely related to TNM stage, cervical lymph node metastasis and clinical stage, which was closely related to the poor prognosis. The results of Western blot and PCR showed that SATB2 was successfully transfected into HN6 cell line and Lv-SATB2-HN6 cells stably overexpressing SATB2 were obtained. The HN6 cells overexpressing SATB2 migrated and the invasive ability was significantly higher than that of HN6 cells. Conclusion：The of SATB2 in oral squamous cell carcinoma and cell line increased, and over of SATB2 could promote the migration and invasion of tumor cells.