Telomerase is a relevant target for cancer therapy. A small 6-mer psoralen-containing oligo-nucleotide is shown to cause efficient photo-cross-linking to human telomere DNA by G-quadruplex formation. The small, photocontrolled oligonucleotide shows effective telomerase inhibition, both in vitro and in vivo, only when light irradiated. Data suggest that it is a promising agent for the treatment of cancer.