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Herein, 7\u2010Dehydrocholesterol (7\u2010DHC), a biosynthetic precursor of cholesterol, as a radiosensitizer, exploiting its ability to propagate the free radical chain reaction is explored. The studies show that 7\u2010DHC can react with radiation\u2010induced reactive oxygen species and in turn promote lipid peroxidation, double\u2010strand breaks, and mitochondrial damage in cancer cells. For efficient delivery, 7\u2010DHC is encapsulated into poly(lactic\u2010<jats:italic>co<\/jats:italic>\u2010glycolic acid) nanoparticles, forming 7\u2010DHC@PLGA NPs. When tested in CT26 tumor bearing mice, 7\u2010DHC@PLGA NPs significantly enhanced the efficacy of radiotherapy, causing complete tumor eradication in 30% of the treated animals. 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