In this work, biogenic ZnO nanoparticles (NPs) were greenly synthesized from Celosia argentea plant extract. Structural analysis confirms the successful synthesis of biogenic Zinc Oxide NPs from C. argentea extract and the produced NPs have average particle size 21.55 ± 4.73 nm with a semispherical shape and specific surface area about 50 m2/g. The biogenic synthesized ZnO NPs showed a powerful radical scavenging activity (Ic50 = 91.24 µg/ml) comparing with ascorbic acid (ASC) as standard (Ic50 = 14.37 µg/ml). Using an agar diffusion disk, the antibacterial efficacy was tested against both
+ 1 gm and − 1 gm bacteria. In gram positive strains, biogenic ZnO NPs had a greater bactericidal impact than gram negative strains in a concentration dependent manner. Anticancer activity against HepG2 was evaluated using MTT assay, the results reflect the concentration dependent cytotoxic effect of biogenic ZnO NPs against HepG2 cells even at low concentrations with Ic50 = 49.45 µg/ml. Using RT-PCR and flowcytometry, the cell cycle and gene expression were analyzed to determine the potential anticancer mechanism. The results showed that biogenic ZnO NPs activate the apoptotic genes NF-κB, CY-C and P53, which start the apoptotic process. These results suggested that C. argentea improved the antioxidant, antibacterial and anticancer activities of ZnO NPs without altering its structural properties, which make it a potential candidate in many of the biomedical applications.