The direct detection of particle dark matter through its scattering with nucleons is of fundamental importance to understand the nature of DM. In this work, we propose that the high-energy neutrino detectors like IceCube can be used to uniquely probe the DM-nucleon cross-section for high-energy DM of $sim$ PeV, up-scattered by the high-energy cosmic rays. We derive for the first time strong constraints on the DM-nucleon cross-section down to $sim 10^{-32}$ cm$^2$ at this energy scale for sub-GeV DM candidates. Such independent probe at energy scale far exceeding other existing direct detection experiments can therefore provide useful insights complementary to other searches.