Drug resistance during tumor progression is a true problem as this is the major reason for the failure of breast cancer therapy. High constitutive activation of nuclear factor kappa B ( NF-kB) has been found in different cancers, creating an environment conducive for chemotherapeutic resistance. Curcumin, one of the most studied chemo preventive agents, is a natural compound extracted from Curcuma longa L. that allows suppression, retardation or inversion of carcinogenesis. Doxorubicin (DOX) is a drug that is widely used for the treatment of a variety of cancers including breast and liver cancers. This study aims to investigate the effect of combination of curcumin with doxorubicin in breast cancer treatment and provide a new suitable method to overcome cancer resistance. Results: We found that administration of curcumin (200mg/kg b.w.) with doxorubicin (1.25 mg/kg b.w.) results in disappearance of tumor cells (EAC) and results in highly significance decrease of NF-kB. An antioxidant effect of curcumin in vivo was observed; our results investigate a significant increase in antioxidant enzymes.. Conclusion: Curcumin has a strong inhibitory activity against tumors. The combination of curcumin with doxorubicin resulted in a synergistic antitumor activity. These results suggest that curcumin can be developed into an adjuvant chemotherapeutic drug to overcome drug resistance of cancer.