Nanomanipulation of single DNA molecules has great potential in fundamental genetic research and clinical analysis, and is a good model system for studying the interfacial effects on physiochemical processes, which occur when manipulating the linear DNA molecules with an atomic force microscope (AFM) tip. Here, we demonstrate that AFM nanomanipulation can be carried out on DNA molecules covered by a single-layered reduced graphene oxide sheet. Nanomanipulation, which includes cutting, pushing, and sweeping operations, specific to the covered DNA molecules can be achieved in a well-controlled manner using AFM in the PeakForce Quantitative Nano-Mechanics mode. It was found that the normal force required to cut covered DNA strands is over five times greater than that required for naked strands. This technique provides a distinctive method for the construction of graphene architecture by tailoring the underlying artificial DNA nanostructures.