Aims: To evaluate the anti breast-cancer activity, biocompatibility and toxicity of poly(d,l)-lactic-co-glycolic acid (PLGA)-encapsulated quercetin nanoparticles (Q-PLGA-NPs). Materials & methods: Quercetin was nano-encapsulated by an emulsion-diffusion process, and the nanoparticles were fully characterized through Fourier transform infrared spectroscopy, x-ray diffractions, FESEM and zeta-sizer analysis. Activity against CAL51 and MCF7 cell lines were assessed by DNA fragmentation assays, fluorescence microscopy, and acridine-orange, and propidium-iodide double-stainings. Biocompatibility towards red blood cells and toxicity towards mice were also explored. Results: The Q-PLGA-NPs exhibited apoptotic activity against the cell lines. The murine in vivo studies showed no significant alterations in the liver and kidney's functional biomarkers, and no apparent abnormalities, or tissue damages were observed in the histological images of the liver, spleen, lungs, heart and kidneys. Conclusion: The study established the preliminary in vitro efficacy and in vivo safety of Q-PLGA-NPs as a potential anti-breast cancer formulation.