When a nanodroplet is placed on a lattice surface, an inhomogeneous surface strain field perturbs the balance of van der Waals force between the nanodroplet and surface, thus providing a net driving force for nanodroplet motion. Using molecular dynamics and theoretical analysis, we study the effect of strain gradient on modulating the movement of a nanodroplet. Both modeling and simulation show that the driving force is opposite to the direction of strain gradient, with a magnitude that is proportional to the strain gradient as well as nanodroplet size. Two representative surfaces, graphene and copper (111) plane, are exemplified to demonstrate the controllable motion of the nanodroplet. When the substrate undergoes various types of reversible deformations, multiple motion modes of nanodroplets can be feasibly achieved, including acceleration, deceleration, and turning, becoming a facile strategy to manipulate nanodroplets along a designed two-dimensional pathway. Copyright © 2019 American Chemical Society.