Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) are typical multifunctional proinflammatory cytokines involved actively in the regulation of immunity, hematopoiesis, inflammation and carcinogenesis. Coordinated regulation of these cytokines could be required for effective regulation of early phase inflammation and cancer progression. The present work was aimed to analyze the anti-carcinogenic action of curcumin on the expression of TNF-α and IL-6 even after withdrawal of treatment. Up-regulated expressions of TNF-α and IL-6 in terms of mRNA and protein levels in lymphoma bearing mice were significantly down-regulated by curcumin as compared to normal. Electrophoretic mobility shift assay (EMSA) results revealed that curcumin reduced binding of nuclear protein with ETS and NF-κB binding elements of TNF-α and IL-6 promoters, respectively. The anti-carcinogenic effect of curcumin against lymphoma progression has been reported previously. In continuation, the present study suggests that the long-term effect of curcumin may contribute to attenuate cancer progression via the down-regulation of TNF-α and IL-6 modulated by E26 transformation-specific protein (ETS) and nuclear factor-κB (NF-κB), respectively.