We have successfully demonstrated the potential of surface-enhanced Raman spectroscopy (SERS) in monitoring the real time damage to genomic DNA. To reveal the capabilities of this technique, we exposed DNA to reactive oxygen species (ROS), an agent that has been implicated in causing DNA double-strand breaks, and the various stages of free radical-induced DNA damage have been monitored by using SERS. Besides this, we showed that prompt DNA aggregation followed by DNA double-strand scission and residual damage to the DNA bases caused by the ROS could be substantially reduced by the protective effect of Pt nanocages and nearly cubical Pt nanopartcles. The antioxidant activity of Pt nanoparticles was further confirmed by the cell viability studies. On the basis of SERS results, we identified various stages involved in the mechanism of action of ROS toward DNA damage, which involves the DNA double-strand scission and its aggregation followed by the oxidation of DNA bases. We found that Pt nanoparticles inhibit the DNA double-strand scission to a significant extent by the degradation of ROS. Our method illustrates the capability of SERS technique in giving vital information about the DNA degradation reactions at molecular level, which may provide insight into the effectiveness and mechanism of action of many drugs in cancer therapy.