Natural compounds such as (-)-epicatechin show a variety of biological properties including anticancer activity. Nonetheless, (-)-epicatechin's therapeutic application is limited due to its low water solubility and sensitivity to oxygen and light. Additionally, previous studies have reported that the encapsulation of flavonoids in nanoparticles might generate stable deliverable forms, which improves the availability and solubility of the bioactive compounds. The aims of this study were to generate (-)-epicatechin-loaded lecithin-chitosan nanoparticles (EC-LCT-NPs) by molecular self-assembly and to assess their cytotoxic potential against breast cancer cells. Various parameters were measured to characterize the EC-LCT-NPs including size, polydispersity index (PdI), zeta potential, morphology and entrapment efficiency. The results showed that the mean particle size of the EC-CLT-NPs was 159 ± 2.23 nm (PdI, 0.189), and the loading and entrapment efficiencies of (-)-epicatechin were 3.42 ± 0.85% and 56.1 ± 3.9%, respectively. The cytotoxic effect of the EC-CLT-NPs was greater than that of free (-)-epicatechin on breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-436 and SK-Br3). Indeed, EC-LCT-NPs showed an IC50 that was four-fold lower (85 μM) than free (-)-epicatechin (350 μM) and showed selectivity to cancerous cells. This study demonstrated that encapsulating (-)-epicatechin into lecithin-chitosan nanoparticles opens new options for breast cancer treatment.