About 98% of the human genome consists of non-coding DNA and more than half harbors repetitive sequences. At the moment, the function of most of these non-coding elements remains elusive despite an association of several of these elements with diseases such as cancer, diabetes and aging-related disorders. This is partly due to the fact that the modern molecular biology toolbox is adapted to research protein-coding genes. The study of protein binders to non-coding DNA sequences and RNA structures is an attractive entry point to examine the function of non-coding elements. To that end, we have established a quantitative mass spectrometry approach to identify proteins binding to nucleic acids. Applying this technique to telomeres, repetitive DNA at the extremity of chromosomes, we identified previously unreported telomeric DNA- and telomeric RNA-binders. Our work serves as a blueprint to functionally dissect additional repetitive elements as well as other important non-coding loci.