AbstractTwo-dimensional (2D) materials possess outstanding lubrication property with their thicknesses down to a few atomic layers, but they are easily susceptible to sliding induced degradation or ubiquitous chemical modification. Maintaining the superior lubricating performance of 2D materials in a harsh working environment is highly desirable yet grandly challenging. Here we show that by proper alignment of graphene on a Ge(111) substrate, friction of graphene could be well preserved at an ultra-low level even after fluorination or oxidation. This behaviour is experimentally found to be closely related to the suppression of molecular-level deformation of graphene within the moiré superlattice structure. Atomistic simulations reveal that the formation of an interconnected meshwork with enhanced interfacial charge density imposes a strong anchoring effect on graphene even under chemical modification. Modulating molecular-level deformation by interfacial confinements may offer a unique strategy for tuning the mechanical or even chemical properties of 2D materials.