The anti-estrogen tamoxifen (Tam) is the most preferred option for patients with estrogen-receptor (ER)-positive breast cancer. However, multi-drug resistance (MDR) is a considerable clinical problem in the successful chemotherapeutic treatment. Members of the ATP-binding cassette (ABC) transporter family proteins play an important role in acquired drug resistance. Many studies have focused primarily on the clinical significance of P-gp (MDR1), BCRP and MRP1 members belong to ABC transporter superfamily on anticancer-drug resistance. Consequently, several strategies have been improved to overcome drug resistance. Nanoparticle drug delivery systems provide an increase in the intracellular concentration of the drugs as well as a reduction in toxicity of free-drug on healthy cells thanks to unique physical and biological properties. Solid lipid nanoparticles (SLNs) have been improved as an alternative colloidal drug delivery systems due to successful incorporation of both hydrophilic and hydrophobic compounds and their related benefits (controlled drug release, high entrapment efficiency and small size etc.) For this purpose, the aim of this study was to discuss the role of Tam-loaded solid lipid nanoparticles (SLNs) to overcome MDR and determine the ability of Tam-SLNs to induce apoptosis.