The widespread use of nanomaterials, such as carbon based 2D nanomaterials, in biomedical applications, has been accompanied by a growing concern on their biocompatibility, and in particular, on how they may affect the integrity of cell membranes. Herein, the interactions between C2N, a novel 2D nanomaterial, and human red blood cell membranes are explored using a combined experimental and theoretical approach. The experimental microscopies show that C2N exerts a negligible hemolysis effect on the blood cells with a superior compatibility to their cell membranes, when compared with the control system, reduced graphene oxide (rGO), which is found to be highly hemolytic. The molecular dynamics simulations further reveal the underlying molecular mechanisms, which indicate that C2N prefers to be adsorbed flat on the water–membrane interface. Interaction energy analyses demonstrate the crucial role of Coulombic contributions, originating from the unique electrostatic potential surface of C2N, in preventing C2N from penetrating into cell membranes. These findings indicate a high compatibility of C2N with cell membranes, which may provide useful foundation for the future exploration of this 2D nanomaterial in related biomedical applications.