Background and Aim: Bismuth and its related compounds such as bismuth oxide nanoparticles (Bi2O3 NPs) are widely used in the medical field of science for drug delivery, cancer therapy, bio imaging, and fighting against pathogenic microorganisms. Most of the chemical compounds used in the synthesis of nanoparticles are toxic to human health and the environment, for this reason, recently considerable interest has been focused on the green synthesis of non-toxic and environmentally friendly nanoparticles (NPs). In the biosynthesis procedure, chemicals reducing agents are replaced by cell extract of organisms that contain bio-reductive compounds as stabilizing and capping agent for NPs. Methods: In this study, bismuth oxide nanoparticles (Bi2O3 NPs) were prepared using green synthesis by cyanobacterial cell extract of Spirulina platensis. The physico-chemical properties of the Bi2O3 NPs characterized by X-ray diffraction (XRD), energy dispersive X‒ray (EDX) analysis, Fourier-transform infrared (FT-IR) spectroscopy, scanning and transmission electron microscopy (SEM). The apoptotic properties of biosynthesized nanoparticles on MCF-7 and MCF-10a cell lines were determined using the effect of the Bi2O3 NPs on the expression of BAX and BCL2 genes by real-time polymerase chain reaction. Results: The size, shape, and morphology of Bi2O3 NPs are suitable for penetrating into the cancer cells and affecting their vital activities. In the MCF-7 cell line, the ratio of BAX/BCL2 expression was significantly higher than that of in MCF-10a cell line treated with the Bi2O3 NPs. Conclusion: The results revealed the stimulation of apoptosis in breast cancer cell line by green synthesized Bi2O3 NPs through an increase in apoptosis regulator genes expression.