Objective: The transformed cells in oral cancer secrete inflammatory mediators which generate an inflammatory microenvironment result in malignant transformation. Nuclear factor-κB (NF-κB) regulates a large number of genes which play a critical roles of the immune, inflammatory responses, cell proliferation, differentiation, and survival. Nanoparticles are 100 to 10,000 times smaller than human cells, could be designed to be highly selective for tumors and allow a slow release of active anticancer agents. We performed this study to investigate the effect of annonaceae nanoparticles and Emetine/Chitosan nanoparticles against scc-25 cell lines human tongue squamous cell carcinoma by studying their effect on NF-κB p65 expression.Methods: Cell Line cells were obtained from American Type Culture Collection, cells were cultured using DMEM (Invitrogen/Life Technologies). The effect of Annonaceae nanoparticles and EMETIN drug were investigated by Enzyme-Linked Immunosorbent Assay. The Signal is generated proportionally to the amount of bound NFĸB p65 and the intensity is measured by ROBONIK P2000 ELISA READER at 450 nm.Results: Treatment of tongue scc-25 cells with both annonacea NP and Emetine/Chitosan NP revealed a significant increase in expression of NFĸB p65 in cancer cells by (227 & 261 pg/ml) respectively at incubation period 48 hours . While the control untreated cancer cells scc-25 revealed lower expression of NFĸB p65 at (147 pg/ml at incubation period 48 hour. Conclusion:Our findings demonstrate that annonaceae and Emetine nanoparticle might have regulatory effect on canonical NF-kb pathway by upregulation of NFĸB p65 expression signals.