The genotoxic potential of anti-tumor drugs limits their efficacy in the treatment of cancers. Since ancient times,saffron (dried stigmas of Crocus sativus L.) has been used as a spice and medicinal herb. Saffron is a rich source of carotenoids and is known for its anti-cancer and antitumor properties. The present study was designed toascertain the chemoprotective potential of saffron against the genotoxicity of three well-known anti-tumor drugs /cisplatin (CIS), cyclophosphamide (CPH) and mitomycin-C (MMC) / using comet assay. Three doses of saffron (20,40 and 80 mg/kg b.w.) were orally administered to mice for five consecutive days prior to the administration ofanti-tumor drugs under investigation. Pre-treatment with saffron significantly inhibited anti-tumor drugs induced cellular DNA damage (strand breaks) as revealed by decreased comet tail length, tail moment and percentDNA in the tail. These findings, together with our previous results, suggest a potential role for saffron as an anti-genotoxic, anti-oxidant and chemopreventive agent and could be used as an adjuvant in chemotherapeutic applications.