Background Evidence suggests that enolase-phosphatase 1 (ENOPH1) is involved in the progression of some certain types of cancers and acts as an oncogenic factor in tumor progression. The present study aimed to identify the central role of ENOPH1 in the progression of breast cancer (BC), a highly proliferative and aggressive disease. Methods and results ENOPH1 expression in BC tissues was explored based on the online resource and 40 paired fresh BC and para-carcinoma samples. Functional assays were performed to evaluate the biological effect of ENOPH1 on cell proliferation and migration in ENOPH1-silenced or overexpressing BC cell lines. Blockade of NF-kappa B by BAY11-7082 was performed to evaluate whether ENOPH1 exerted tumor-promoting properties via regulating the NF-kappa B signaling pathway. Results of the present study demonstrated that ENOPH1 expression was profoundly upregulated in BC tissues compared with adjacent breast tissues, and ENOPH1 expression was associated with cancer stage, node metastasis status, and overall survival. Functional assays demonstrated that ENOPH1 overexpression significantly accelerated BC cell proliferation, migration, and invasion, while genetic knockdown of ENOPH1 yielded the opposite effects. Mechanistically, ENOPH1 activated the NF-kappa B pathway, as evidenced by increased expression of NF-kappa B downstream genes and enhanced NF-kappa B p65 nuclear translocation. Furthermore, the oncogenic properties of ENOPH1 in proliferation, migration, and invasion were restrained following inhibition of the NF-kappa B signaling pathway. Conclusions These findings indicated the significance of ENOPH1 in promoting cell proliferation and invasion, mainly through activating the NF-kappa B pathway, suggesting that ENOPH1 might be an attractive prognostic factor and a potential target for BC therapy.