The tip-membrane interface plays a critical role in characterizing the mechanical properties of ultrathin 2D materials by commonly employed nanoindentation based on atomic force microscopy (AFM). However, the reliability of the assumption that the tip-membrane interface remains pinned during nanoindentation remains unclear, which may introduce unignorable uncertainty in evaluating their true mechanical properties. In this work, it is reported that load-dependent frictional behavior would occur on the tip-membrane interface during nanoindentation tests on monolayer and multilayer suspended WS2 and graphene, and the curve hysteresis could be well explained by the stick-slip behavior. Further analyses and finite element simulations demonstrated that the frictional energy dissipation should be mainly attributed to the frictional behavior along the direction parallel to the cantilever beam. Meanwhile, the in-plane membrane stiffness was mainly responsible for the different frictional behavior on monolayer and multilayer 2D materials. Based on these analyses, some suggestions were proposed to help reduce the uncertainty when extracting the mechanical properties of 2D materials. These findings not only facilitate the deep understanding of the origin of the curve hysteresis during nanoindentation, but also help to evaluate the mechanical properties of 2D materials in a more reliable way.