In order to overcome the limitations of conventional therapeutic systems in the treatment of cancer, nanoparticles (NPs) have been rapidly produced and developed as a sep. treatment method for control of cancer. Synthesis of nanoparticles using plant-based materials (green synthesis), due to the easy and cost-effective synthesis, production of non-toxic, sustainable and environmentally friendly products, can be considered the most appropriate method for preparation of NPs. In this study, after synthesis of Bi2O3 NPs using Ginger (Zingiber officinale) root (rhizome) extract, the synthesized NPs were characterized and their potential application as selective anticancer agents against HCT116 colorectal cancer cells was evaluated through regulation of PI3K/AKT/mTOR signaling pathway, whereas the human kidney (HK-2) cells were used as normal cells. FTIR anal. showed a band at 673 cm-1 attributed to Bi-O vibration with a fingerprint region at 1291 cm-1 demonstrating the attachment of the organic mols. to the synthesized Bi2O3 NPs. UV-visible study showed a λmax of around 268 nm, whereas XRD anal. showed eight clear peaks, demonetizing the crystalline phase of synthesized Bi2O3 NPs. TEM anal. showed that spherical-shaped Bi2O3 NPs have a size range of 20-50 nm with a man size of around 35 nm. Finally, DLS anal. determined that Bi2O3 NPs have a hydrodynamic size of about 71.19 nm (PDI of 0.179) and a zeta potential value of -44.39 mV, revealing the good colloidal stability of NPs. Cellular assays (MTT, LDH, flow cytometry, and RT-qPCR) showed that synthesized Bi2O3 NPs selectively induced anticancer effects against HCT116 colorectal cancer cells through membrane leakage, generation of ROS, induction of apoptosis via dysregulation of Bax, Bcl-2 and caspase-3 at mRNA level mediated via regulation of PI3K/AKT/mTOR signaling pathway. In conclusion, it may be suggested that the presence study could provide useful information for the potential anticancer effects mediated by synthesized Bi2O3 NPs in vitro, although further studies, including in vivo studies and clin. trials, are needed to support our findings.