Cadherin 11 (CDH11) expression is detected only in invasive breast cancer cells and aggressive breast cancer specimens. However, little is known about the molecular mechanisms of CDH11 transcriptional regulation. Here, we report that interleukin enhancer binding factor 3 (ILF3) interacts with Homeobox C8 (HOXC8) to activate CDH11 transcription in breast cancer cells. Using co-immunoprecipitation and mass spectrometry analyses, ILF3 is shown to interact with HOXC8 in breast cancer cells. We demonstrate that ILF3 binds to the CDH11 promoter on nucleotides -2982 similar to -2978 and -2602 similar to 2598 and interacts with HOXC8 to co-activate CDH11 transcription. We further show that ILF3 promotes proliferation and migration, at least partially, by facilitating CDH11 expression in breast cancer cells. Moreover, immunohistochemistry (IHC) shows that expression of CDH11, ILF3 and HOXC8 are all upregulated in breast cancer specimens compared to normal breast tissues. Importantly, the expression levels of CDH11, ILF3 and HOXC8 are elevated in the advanced stages of breast cancer, and high expression of CDH11, ILF3 and HOXC8 is associated with poor distant metastasis-free survival (DMFS) for breast cancer patients.