Ionising radiation (γ or X-rays) is the mandatory tool to treat cancer despite its detrimental effects in particular on skin cells which lead to severe dermatological diseases and carcinogenesis. Natural antioxidants caffeic acid (CA), rosmarinic acid (RA), trans cinnamic acid (TCA), p-coumaric acid (PCA), and hydroxyphenyllactic acid (HPA) acid are known to be potent anticancer and antioxidant agents. Current study is designed to provide experimental evidence as these compounds offer radiation protection for skin cells. Non-toxic concentrations of CA, RA, TCA, PCA, and HPA were tested for radiation protection, γ-radiation induced intracellular reactive oxygen species (ROS) by flow cytometry and DNA double strand break in human keratinocytes (HaCaT cells) by immunocytochemistry. CA, RA and TCA pretreatment can protect the HaCaT cells by 40%, 20%, 15% respectively through scavenging γ-radiation induced ROS and decreasing number of post irradiation 53bp1 foci. Inclusion of these compounds in chemo-radiotherapy could facilitate to achieve multiple target protection (i.e. anti-cancer and skin radio protectant).