Background: The nuclear factor kappa-B (NF-kappa B) is a major transcription factor responsible for the production of numerous inflammatory mediators, including the tumor necrosis factor (TNF alpha), which has a lethal association with cancer's onset. The silver nanoparticles (AgNPs) are widely used in cancer treatment and several other biomedical applications.Objective: The study aimed to determine the effects of silver citrate nanoparticles (AgNPs-CIT) on NF-kappa B activation together with TNF alpha mRNA/protein expressions in the phorbol myristate acetate (PMA)-stimulated MCF-7 human breast cancer cell-lines.Methods: The AgNPs-CIT were synthesized by the reduction method, and the prepared AgNPs-CIT were characterized for their shape, absorption in UV-VIS electromagnetic radiations, size distribution, zeta-potential, and antioxidant activity. The MCF-7 cell-lines were pretreated with AgNPs-CIT and stimulated with PMA. The TNF alpha mRNA expressions were determined by real-time PCR, whereas the protein production was determined by the ELISA. The NF-kappa B activity was distinctly observed by highly-specific DNA-based ELISA, and by NF-kappa B-specific inhibitor, Bay 11-7082.Results: The prepared AgNPs-CIT were spherical and have an absorption wavelength range of 381-452 nm wherein the particles size ranged between 19.2 +/- 0.1 to 220.77 +/- 0.12 nm with the charge range -9.99 +/- 0.8 to -34.63 +/- 0.1 mV. The prepared AgNPs-CIT showed comparative antioxidant activity at >40% inhibitions level of the DPPH radicals. The AgNPs-CIT were found to be non-toxic to MCF-7 cell-lines and inhibited PMA-induced activation of the NF-kappa Bp65, and also the mRNA/protein expression of TNF alpha.Conclusion: This is the first report that showed AgNPs-CIT inhibited TNF alpha expression via deactivation of the NF-kappa B signaling event in stimulated breast cancer cells. The results have important implications for the development of novel therapeutic strategies for the prevention/treatment of cancers and/or inflammatory disorders.