The 1.7 kb DRAIC long noncoding RNA inhibits tumor growth, inhibits cancer cell invasion, migration, colony formation and interacts with IKK (IκB kinase) subunits, inhibiting the phosphorylation and degradation of the NF-κB inhibitor, IκB, to suppress the activation of NF-κB. Whether these activities are all linked is unclear. We used SHAPE-MaP to obtain the secondary structure of the lncRNA to perform structure-functions studies which identified the minimal region of DRAIC necessary for repressing NF-κB. A 36-nucleotide hairpin (A+B) within DRAIC inhibits NF-κB, inhibits IκB phosphorylation and binds specifically with the IKKα coiled- coil domain with a very high affinity: K D of ∼1-5 nM. This interaction weakens the dimerization of of the coiled coil domains of two IKK subunits, a dimerization that is indispensable for IKK activity. A+B is sufficient and necessary to inhibit the oncogenic phenotypes in multiple cancer cell-lines, demonstrating that interaction with IKK and inhibition of NF-κB is key for cancer suppression by DRAIC. Presence of this critical hairpin is modulated by alternative splicing the extends exon 4 to exon 4a of DRAIC and the expression of exon 4a in lung tumors is associated with low NF-κB activity. This is also the first demonstration that a short RNA can disrupt coiled- coil dimerization.