Many important physical, chemical, and biological processes taking place in nanoscopic confined water environments may behave very different from that in bulk. In this paper, we report an unusual nonenzymatic degradation of DNA molecules in the confined water nanofilm on mica substrate. We found that the half-time of DNA in the degradation process in the water nanofilm is about several hours under high RH at temperatures ranging from 10 to 50 degrees C, which is much faster than that in bulk water, similar to 10(11) years at 25 degrees C. Careful analysis indicated that it was the formation of a water/vapor interface in the water nanofilm that played a major role in promoting DNA degradation.