Purpose: The resistance to 5-FU often limits its clinical effectiveness on breast cancer treatment. Combination therapy thus is employed to overcome this treatment resistance. We here report a potent antitumor effect of Emodin at low dose on chemotherapy sensitivity of MCF-7 breast cancer cells. Methods: Cell viability, apoptosis, glutathiones (GSH) concentration and Reactive oxygen species (ROS) activity following Emodin and 5-FU treatment was assessed. Cellular senescence following combined treatment and silence of NRARP was examined by senescence-associated beta-galactosidase analysis. Western blot analysis was used to determine changes in the expression of p21, p16, p27, E2F1 and NRARP. Results: Low dose Emodin potentiates 5-FU-induced apoptosis of breast cancer cells, in association with inhibition of NRARP, resulting in cellular senescence. RNA interference of NRARP induced cellular senescence in MCF-7 breast cancer cells. Furthermore, the cellular senescence induced by Emodin and 5FU treatment could be reverted by pcDNA-NRARP. Conclusion: These findings provide preclinical evidence for repurposing use of Emodin in combination with chemotherapeutic agents to treat breast cancer as an alternative salvage regimen. (C) 2018 The Authors. Published by Elsevier Inc.