Abstract: This paper studies the biomechanical behaviors of a red blood cell (RBC) by nanoindentation technique and finite element simulation. The Young's modulus and load-displacement curve of RBC are measured by nanoindentation. Then a 3D finite element model of RBC is built to simulate the naoindentation process. The load-displacement curves of RBC are obtained by altering friction coefficients between the tip and curvature radius of the tip. It is shown that the FEM results are agreement with the experimental data for nanoindentation of RBC. The deformation of RBC is obviously influenced by the curvature radius of the tip but slightly by the friction coefficient between the tip and the cell.