Background and Objective: Breast cancer is the most common cancer among women worldwide. Saffron is one of the most well-known plants as an antioxidant and anticancer. The aim of this study was to assess the impact of saffron on the viability of breast cancer cells and simultaneous interaction effect of Paclitaxel drug. Materials and Methods: In this study, saffron extract (Crocus sativus L.) was prepared by Soxhlet method. Breast cancer cells (4T1) were prepared from the Pasteur cell bank then passaged several times until the required number of cells obtained. Cytotoxicity of Paclitaxel and the extracts of saffron were assessed separately and simultaneously using colorimetric MTT assay and trypan Blue test with certain concentrations of drug and extracts in the treatment period of 48 and 72 h. Then, the rate of apoptogenic changes in each compound was evaluated by Hoechst and PI methods. Results: Data from 48 and 72 h treatment of extract of Crocus sativus showed antitumor effects on breast cancer cells. These effects were dose and time dependent. The synergistic effects in 48 hour treatment indicated a significant increase in cytotoxicity of saffron/Paclitaxel (P <0.05). Conclusion: The results showed that ethanol and aqueous extract of saffron and Paclitaxel have significant anticancer properties against breast cancer cells. It was also found that the aqueous and ethanol extracts of saffron can considerably increase cytotoxicity in cancer cells induced by Paclitaxel while the aqueous extract of saffron showed better results. Referenses 1- Abdullaev Fl. Cancer chemoperventive and tumoricidal properties of saffron. Biol Med. 2002 227: 20-25. 2- Eisenberg D, Kessler R. Saffron redgold of brackish. Tehran Agricultural Information Bank. 1995. 3- Akhondzadeh S, Tahmacebi-Pour N, Noorbalaa A, et al. Crocus sativus L. 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