Ionizing radiation, including that evoked by gamma (${gamma}$)-rays, induces oxidative stress through the generation of reactive oxygen species, resulting in apoptosis, or programmed cell death. This study aimed to elucidate the radioprotective effects of hyperoside (quercetin-3-O-galactoside) against ${gamma}$-ray radiation-induced apoptosis in Chinese hamster lung fibroblasts, V79-4 and demonstrated that the compound reduced levels of intracellular reactive oxygen species in ${gamma}$-ray-irradiated cells. Hyperoside also protected irradiated cells against DNA damage (evidenced by pronounced DNA tails and elevated phospho-histone H2AX and 8-oxoguanine content) and membrane lipid peroxidation. Furthermore, hyperoside prevented the ${gamma}$-ray-provoked reduction in cell viability via the inhibition of apoptosis through the increased levels of Bcl-2, the decreased levels of Bax and cytosolic cytochrome c, and the decrease of the active caspase 9 and caspase 3 expression. Taken together, these results suggest that hyperoside defend cells against ${gamma}$-ray radiation-induced apoptosis by inhibiting oxidative stress.