Abstract: To investigate the correlation among the nuclear respiratory factor-1 ( NRF-1 ) expression and the carcinogenesis, invasion, metastasis, as well as Ki-67 expression, in breast cancer. Methods: NRF-1 and Ki-67 expression in 211 cases with breast cancer and 50 with benign lesion of the mammary gland were determined with immunohistochemical EnVision indirect method. Results: NRF-1 was located at the nucleus. The positive rates of NRF-1 expression were 82.7% in breast cancer and 100% in benign lesion of the mammary gland ( χ2 = 100.288, P = 0.000 ). NRF-1 expression rates were significantly higher in well-differentiated breast cancer than those in the moderately and poorly differentiated breast cancers ( χ2 = 16.242, P = 0.001; χ2 = 72.802, P = 0.000, respectively ). In addition, NRF-1 expression was higher in the moderately differentiated breast cancer than in the poorly differentiated breast cancer (χ2 = 30.190, P = 0.000 ). NRF-1 expression was lower in the patients with nodal metastasis than that in patients without a similar condition ( χ2 = 12.025, P = 0.007). The positive rate of NRF-1 was significantly lower in the TNM II and III stages than in the TNM I stage ( χ2 = 12.025, P = 0.007). The positive rate of Ki-67 was 78.7% in 211 patients with breast cancer. There were significant differences among the Ki-67 and NRF-1 expression rates ( χ2 = 42.914, P = 0.000), pathohistological grade ( χ2 = 40.239, P = 0.000), nodal metastasis ( χ2 = 16.061, P = 0.001), and TNM staging ( χ2 = 13.589, P = 0.004). Conclusion: NRF-1 expression plays an important role in the occurrence, as well as development, of breast cancer and correlates with Ki-67 expression. NRF-1 expression can be a marker in the progression and prognosis of breast cancer and may be used as the target for clinical treatment.