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Introduction: TNF-α/NF-kB signaling pathway plays an important role in promoting the inflammatory process and growth of breast cancer. Accordingly, the aim of the present study was to investigate the synergistic combination effect of endurance exercise with curcumin on breast cancer progression through TNF-α/NF-kB signaling axes in female BALB/c mice with breast cancer. Methods: The design of the present study was experimental. After transplanting 4T1 breast cancer into the right flank of 40 BALB/c mice, all mice were randomly divided into four groups, including endurance training (E), endurance training-curcumin (EC), curcumin (CC), and control (C). Then, E and EC groups (5 days per week) were performed for 5 weeks. Curcumin (6 times per week) was given by gavage to EC and CC groups for five weeks. The intratumoral expression of TNF-α and NF-kβ were measured using the qRT-PCR method. One-way analysis of variance and LSD post hoc test with SPSS version 16 were used for statistical analysis. P< 0.05 was considered statistically significant. Results: A significant decline in cancer growth and the gene expression of NF-kβ and TNF-α was observed in E, CC, and EC compared to the C group (P =0.001). Furthermore, a significant decline in expression of both genes was observed in EC compared with E. Conclusion: Endurance training combined with curcumin supplementation has a more effective role in reducing TNF-α and NF-κβ, and slowing the growth of breast cancer cells when compared with either of other interventions alone.