Combination therapy is considered a viable strategy to overcome the resistance to chemotherapeutics. Survivin as a member of the inhibitor of apoptosis protein (IAP) family, which is involved in resistance to various drugs. We investigated the role of combination therapy in downregulating survivin and increasing drug's efficacy in MDA-MB-231 cells. MTT assay and DAPI staining were applied to study the anti-proliferative activity and apoptosis response of the agents. Real-time RT-PCR and Western blot analysis were applied to study survivin mRNA and protein. Our findings showed that combined treatment of cells with docetaxel and vinblastine reduces survivin expression and consequently decreases the IC50 value of docetaxel from 70 to 5 nM (p < 0.05). Furthermore, combination therapy with deguelin, a survivin inhibitor, exerted a considerable enhancement in synergistic efficacy of docetaxel and vinblastine (p < 0.05). Survivin downregulation may thus be considered a potential strategy in increasing the efficacy of chemotherapeutics in cancer patients.