In the realm of nanotechnology, atomically thin two-dimensional graphene has garnered attention for its impeccable hexagonal physical structure and chemically inert surface properties. These attributes endow graphene with remarkable mechanical, physical, and chemical characteristics, positioning it as one of the ideal solid lubricants for mitigating friction and wear at contact interfaces. However, the performance of graphene is intricately linked to the substrate it interacts with. Consequently, an in-depth investigation of how substrate variations impact graphene's friction behavior assumes paramount significance in the realm of industrial applications. This study delves into the intricate dynamics of graphene friction through atomic force microscopy experiments, focusing on three pivotal aspects: the binding strength between graphene and the substrate, the Young’s modulus of the substrate, and substrate materials. By subjecting the SiO2/Si substrate to plasma treatment to augment its surface energy, we enhance the interface binding strength between the substrate and graphene, thereby diminishing friction on the graphene surface. Furthermore, we investigate how graphene responds to various substrates, including polypropylene carbonate films of varying Young’s modulus, as well as graphite, h-BN, and SiO2/Si substrates. Graphene demonstrates a pronounced inclination toward increased friction when interfacing with substrates characterized by lower Young's modulus, higher roughness, and adhesion. These findings elucidate the potential for fine-tuning friction in lamellar materials, underscoring the pivotal role of comprehending nanoscale friction dynamics on graphene surfaces.