By ESR spin elimination and photodeavage assay, the mechanisms of one-electron oxidation damage of oligonucleotides by excited triplet state of riboflavin (Rb) have been elucidated. The results demonstrate that Rb, an endogenous photosensitizer, is capable of cleaving single-stranded telomeric overhang and the template region of telomerase RNA under UVA irradiation, resulting in blocking of reverse transcription of telomeric DNA which leads to the apoptosis of cancer cells ultimately.