Manipulation of an isolated water nanodroplet (WN) on certain surfaces is important to various nanofluidic applications but challenging. Here we present a digital nanofluidic system based on a graphene/water/mica sandwich structure. In this architecture, graphene provides a flexible protection layer to isolate WNs from the outside environment, and a monolayer ice-like layer formed on the mica surface acts as a lubricant layer to allow these trapped WNs to move on it freely. In combination with scanning probe microscope techniques, we are able to move, merge, and separate individual water nanodroplets in a controlled manner. The smallest manipulatable water nanodroplet has a volume down to yoctoliter (10(-24) L) scale.