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Despite significant advances in early detection and personalized treatment, cancer is still among the leading causes of death globally. One of the possible anticancer approaches that is presently receiving a lot of attention is the development of nanocarriers capable of specific and efficient delivery of anticancer drugs. Graphene-based materials are promising nanocarriers in this respect, due to their high drug loading capacity and biocompatibility. In this review, we present an overview on the interactions of graphene-based materials with normal mammalian cells at the molecular level as well as cellular and subcellular levels, including plasma membrane, cytoskeleton, and membrane-bound organelles such as lysosomes, mitochondria, nucleus, endoplasmic reticulum, and peroxisome. In parallel, we assemble the knowledge about the interactions of graphene-based materials with cancerous cells, that are considered as the potential applications of these materials for cancer therapy including metastasis treatment, targeted drug delivery, and differentiation to non-cancer stem cells. We highlight the influence of key parameters, such as the size and surface chemistry of graphene-based materials that govern the efficiency of internalization and biocompatibility of these particles in vitro and in vivo. Finally, this review aims to correlate the key parameters of graphene-based nanomaterials specially graphene oxide, such as size and surface modifications, to their interactions with the cancerous and non-cancerous cells for designing and engineering them for bio-applications and especially for therapeutic purposes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)