In this study, we found that TGF-B activates the NF-kB pathway. Inhibition of NF-kB signaling markedly abrogates TGF-B-induced EMT. By studying the regulatory mechanism of TGF-B-induced NF-kB signaling, we found that lncRNA NKILA was upregulated by TGF-B and was essential for the negative feedback regulation of the NF-kB pathway. Accordingly, overexpression of NKILA significantly reduced TGF-B-induced tumor metastasis in vivo. Consistent with the results from mice, the expression of NKILA was negatively correlated with EMT phenotypes in clinical breast cancer samples. Collectively, our study findings indicated that the NKILA-mediated negative feedback affects TGF-B-induced NF-kB activation and that NKILA may be a therapeutic molecule in breast cancer metastasis via inhibition of EMT.