Objectives: To explore the expression and clinical significance of Sema4A in triple-negative breast cancer. Methods: Eighty patients with invasive ductal carcinoma of the breast and 40 normal tissues adjacent to cancer were selected. Immunohistochemical methods were used to detect the expression of Sema4A in breast cancer and normal tissues adjacent to cancer, and its relationship with breast cancer clinicopathological features and prognosis. Results: The expression of Sema4a in the serum of BCA patients was significantly higher than that of healthy controls. In addition, the expression of sema4a in BCA cells and in the cell supernatants was also up-regulated under hypoxia. Conclusion: Exogenous Sema4A can protect BCA cells from hypoxia-induced cytotoxicity, inhibit cell apoptosis and promote cell proliferation.