© 2021 The American Ceramic SocietyZinc-doped hydroxyapatite (HA) nanoparticles were synthesized by microwave assisted method and used with ionizing radiation for inhibition of proliferation of breast cancer cells. Zinc-doped HAs were produced in four different compositions in order to determine the best doping rate in terms of physical and biological properties. Nanoparticle characterizations were performed with X-ray diffractometer, Fourier transform infrared spectroscopy, scanning electron microscopy, and inductively coupled plasma-mass spectrometry. Viability of MDA-MB-231(isolated at M D Anderson from a pleural effusion of a patient with invasive ductal carcinoma) cells treated with nano-HA particles and radiation were assessed by MTT assay. Caspase-7 and Poly (ADP-ribose) polymerase protein expressions in samples were examined by the Western blot. X-ray diffraction patterns of our samples were found to be in good correlation with the reference HA peaks. Notably, increasing zinc amount resulted in elevated percentage of β-tricalcium phosphate, phases. All formulations including pure HA particles were non-cytotoxic in MDA MB 231 cells. On the other hand, low rate Zn-doped HA particles showed significant anti-proliferation effect during irradiation. The combination of irradiation with Zn-doped HA particles also induced apoptosis, demonstrated as cleavage of caspase-7 and PARP proteins. In conclusion, low rate Zn-doped HA enhanced the radiation effect on breast cancer cells.