Objective: To investigate the expression of UCH-L3 and HIF-1α in breast cancer, cancer adjacent tissues and benign lesions and their relationships with the clinicopathological characteristics. Methods: Immunohistochemistry (IHC) method was used to detect the expression of UCH-L3 and HIF-1ɑ in 99 cases with breast cancer, 38 cases with cancer adjacent tissues and 29 cases with benign lesions. Results: (1) The positive expression rate of UCH-L3 in breast cancer tissue was significantly lower than that in the cancer adjacent tissues, and the expression intensity was significantly weaker than that in cancer adjacent tissues and benign lesion tissue (P<0.05). (2) The basal cell like subtype was significantly lower than that of luminal A subtype (P<0.05). (3)The expression intensity of UCH-L3 in breast cancer was positively correlated with ER and PR expression (P<0.05). (4)The nuclear expression rate of HIF-1α in the breast cancer was significantly higher than that in the cancer adjacent tissues and benign lesions. In luminal typing, the nuclear expression rate of HIF-1α in the HER2 overexpression subtype and basal cell like subtype was significantly higher than that of luminal A and B; The intensity of nuclear expression was positively correlated with Ki-67 expression proportion and histological grade, and negatively correlated with ER and PR protein expression (P<0.05). (5)The rate of HIF-1α cytoplasmic expression in the breast cancer was significantly higher than that in the cancer adjacent tissues. According to the Luminal Type, the basal cell like subtype was significantly lower than that in luminal A/B and HER2 overexpression subtype. The expression intensity was negatively correlated with Ki-67 and histological grade, and positively correlated with ER, PR and UCH-L3 expression intensity (P<0.05). Conclusions: Lost expression of UCH-L3 and overexpression of HIF-1α might play a role in the oncogenesis and the development of breast cancer. The transformation of HIF-1α from cytoplasm into nucleus indicates the malignant evolution of tumor. UCH-L3 and HIF-1α have certain value in the prognosis evaluation of breast cancer. To increase the expression of UCH-L3 and to prevent the migration of HIF-1α from cytoplasm to nucleus may be helpful for the prevention and treatment of breast cancer, especially for basal cell like breast cancer.