NF-kB is a critical link between inflammation and cancer, but whether long non-coding RNAs (IncRNAs)regulate its activation remains unknown.Here, we identify an NF-KappaB Interacting LncRNA (NKILA),which is upregulated by NF-kB, binds to NF-kB/IkB, and directly masks phosphorylation motifs of IkB,thereby inhibiting IKK-induced IkB phosphorylation and NF-kB activation.Unlike DNA that is dissociated from NF-kB by IkB, NKILA interacts with NF-kB/IkB to form a stable complex.Importantly, NKILA is essential to prevent over-activation of NF-kB pathway in inflammation-stimulated breast epithelial cells.Furthermore,low NKILA expression is associated with breast cancer metastasis and poor patient prognosis.Therefore,IncRNAs can directly interact with functional domains of signaling proteins, serving as a class of NF-kB modulators to suppress cancer metastasis.