Synthesis of nanoparticles (NPs) from common food waste is an eco-friendly and cost-effective method. The present communication reports one-pot biosynthesis of silver nanoparticles (AgNPs) from Citrus sinensis (orange) peel extract (OPE). A clear synthesis of monodispersed AgNPs with average size of 22 nm has been indicated by UV–Vis spectrophotometry, dynamic light scattering and transmission electron microscopy and X-ray diffraction techniques. On the other hand, FTIR study clearly revealed that ‘ether’ and ‘alcoholic’ groups are mainly responsible for the stabilization of AgNPs. Theoretical simulation using density functional theory showed that among the alcoholic and ether groups, hotrienol is primarily responsible for the stabilization of AgNPs with the highest interaction energy of 62.92 kJ/mol. Synthesized AgNPs were found to induce apoptosis in model system hepatocellular carcinoma cell, Hep3B and showed increased percentages of late apoptotic cells. © 2020, Institute of Chemistry, Slovak Academy of Sciences.