Objective:To investigate the role of cyclo-oxygenase-2 (COX-2) in breast cancer metastasis and its possible mechanism. Methods: A total of 45 cases of primary breast cancer tissues and brain metastatic breast cancer tissues were collected from patients, who underwent mastectomy in Yunnan Cancer Hospital from October 2015 to April 2018, including 30 cases of primary lesions and 15 cases of brain metastasis. qPCR was used to detect the expression of COX-2 in breast cancer tissues and brain metastatic breast cancer tissues. Recombinant viruses with COX-2 over-expression (LV6-COX2) or COX-2 knockdown (LV3-COX2 shRNA1, LV3-COX2 shRNA2) were transfected into human breast cancer MDA-MB-231 cells; After obtaining the stable expression cell lines, the effect of COX-2 expression on the proliferation of MDA-MB-231 cells was detected by CCK-8, and the effects of COX-2 expression on the migration and invasion of MDA-MB-231 cells were detected by scratch test and Transwell assay, respectively. The mRNAand protein expressions of COX-2 in each group were examined by qPCR and WB, respectively. The effect of COX-2 expression on the expression of EMT-related genes in MDA-MB-231 cells was analyzed by qPCR. Results: The expression of COX-2 in tissues of patients with brain metastases was significantly higher than that in patients with primary breast cancer tissues (P<0.01), and it was correlated with tumor TMN stage in breast cancer patients. MDA-MB-231 cell lines with stable COX-2 over-expression/knockout were successfully constructed. Over-expression of COX-2 promoted the migration and invasion of MDA-MB-231 cells (all P<0.01), and significantly increased the expressions of MMP2, MMP1, N-cadherin and vimentin (all P<0.01), but exerted insignificant effect on cell proliferation. The effect of COX-2 silence exerted the opposite effect and promoted cell proliferation (P<0.05). Conclusion: COX-2 is highly expressed in brain metastatic breast cancer tissues, which may promote the migration and invasion of breast cancer MDA-MB-231 cells by regulating EMT processes.