How to induce nanoscale directional motion via some intrinsic mechanisms pertaining to a nanosystem remains a challenge in nanotechnology. Here we show via molecular dynamics simulations that there exists a fundamental driving force for a nanoscale object to move from a region of lower stiffness toward one of higher stiffness on a substrate. Such nanoscale directional motion is induced by the difference in effective van der Waals potential energy due to the variation in stiffness of the substrate; i.e., all other conditions being equal, a nanoscale object on a stiffer substrate has lower van der Waals potential energy. This fundamental law of nanoscale directional motion could lead to promising routes for nanoscale actuation and energy conversion.