Background: Non-coding RNAs are increasingly investigated and have great potential for diagnose, prognosis and treatment of cancer. Thus, we investigated the possible relation between NF-κB suppressor-NKILA and HSP90, NF-κB and β-catenin molecules in the MCF-7. HSP90 is a compelling stress protein and together with β-catenin and NF-κB molecules it can be responsible for the cancer cell development. However, NKILA is a novel molecule and there is not comprehensive data about it unlike HSP90, β-catenin and NF-κB alone. Therefore, we suggest that there might be a correlation between NKILA and these proteins. Methods and Results: To investigate the NKILA role on these proteins we inhibited the NKILA by using transfection. MCF-7 cells transfected with NKILA-siRNA and incubated for 5 hours. Then, cells were collected and proteins were extracted to be separated in SDS-PAGE. Aforementioned proteins of siRNA transfected group were evaluated by comparing their band intensities with the control group protein bands by immunoblotting. According to this, HSP90 and NF-κB/p105, NF-κB/p65 and NF-κB/p50 subunits significantly increased while β-catenin significantly decreased after NKILA inhibition.Conclusion:, For the first time we demonstrate that HSP90 and beta-catenin is associated with NKILA levels and this may highly related with canonical NF-κB pathway in MCF-7 cells. These novel findings may have important implications in cancer cells development and might present important hints for the future studies about the cancer cell targeted therapy.