Objective To numerically simulate the specific deformation and calculate the critical pressure of red blood cells in the osmosis experiment. MethodsThe shell model of red blood cells was established. Based on the constitutive hyperelastic model of the form Neo-hookean strain-energy potential and the experimental data for shear modulus of cell membrane provided by references, the red blood cell osmosis model was calculated in finite element software ABAQUS. Results The whole phases of red blood cell deformation when subjected to osmotic pressure were obtained. It was found that cell membrane rapidly changed from biconcave shape to oval shape when osmotic pressure was increased to 50-60 mPa, with the value of critical pressure falling in the scope provided by references. Meanwhile, the Mises stress distributions of cell membrane in different phases were also obtained. Conclusions The critical pressure for red blood cells changing from biconcave shape to oval shape is 50-60 mPa. The shell model and the constitutive hyperelastic model of the form Neo-hookean strain-energy potential can be used in the simulation of the osmosis experiment to provide a clear and reasonable phase of red blood cell deformation.