Objective: To investigate the expression and clinical significance of hypoxia inducible factors HIF-1a, Gli-1 and MMP9 in 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 HIF-1a, Gli-1 and MMP9 in breast cancer and normal tissues adjacent to cancer, and their relationship with clinicopathological features of breast cancer and prognosis was explored. Results: The positive rates of HIF-1a, Gli-1 and MMP9 in breast cancer tissues were significantly higher than those in normal breast tissues. HIF-1a, Gli-1 and MMP9 expressions are positively correlated in breast cancer. Conclusion: HIF-1a, Gli-1 and MMP9 proteins are involved in the pathogenesis of breast cancer.