Objective: The aim of this study was to observe the expressions and clinical significance of HIF-1α in breast cancer and precancerous lesions, and analyze the relationship between the expressions and clinicopathological features in breast cancer. Methods: We analyzed the HIF-1α expression in 128 cases of invasive ductal carcinomas, 146 precancerous lesions patients including 89 cases of ductal carcinoma in situ and 57 cases of atypical ductal hyperplasia. 53 cases of usual ductal hyperplasia breast tissues were selected as a control group. The specimens were evaluated for HIF-1α, estrogen re-ceptor (ER) & progesterone receptor (PR), epidermal growth factor receptor type 2 (HER2/neu) and Ki-67. Immunoreactivity was semi-quantitatively evaluated in at least 1000 cells examined under the microscope at 40 × magnification and recorded as the percentage of positive tumor cells over the total number of cells examined in the same area. The percentage scores were subsequently categorized. The express of HIF-1α and their relationship with multiple biological parameters including ER& PR, HER2/neu and Ki-67, the biomarkers levels of CA153, CA125 TSGF, and CEA in blood serum and nipple discharge, histological grade, region lymph node metastasis, distant metastasis and recurrence on files were also assessed. Results:Compared with usual ductal hyperplasia, the positive expression rate of HIF-1α in atypical ductal hyperplasia, ductal carci-noma in situ and invasive ductal carcinomas group was significantly increased (P 14% groups, histological grade (I + II) and grade III invasive ductal carcinomas groups, with lymph node metastasis, distant metastasis and recurrence groups (P50 years), tumor diameter (≤ 2 cm vs > 2 cm; P > 0.05). The nipple discharge and serum levels of CA153, TSGF, CA125 and CEA in invasive ductal carcinomas HIF-1α positive patients were significantly higher than those in the negative patients (P