Abstract: The study of micromechanical behavior during tablet pressing is often limited to phenomenological studies, accurate calibration of the discrete element model parameters of binary particles is a prerequisite for conducting modeling research on tablet compression. In this study, we take pregelatinized starch and microcrystalline cellulose as the research objects, and apply the Edinburgh elasto-plastic adhesion (EEPA) contact model to establish a discrete elemental simulation model for binary material pressing. Taking tablet force-hardness and force-volume reduction as response values, the optimal values of the discrete meta-parameters that significantly affect tablet pressing are obtained by applying Plackett-Burman design, Latin hypercubic sampling, Kriging model, and Non-dominated Sorting Genetic Algorithm (NSGA-Ⅱ) calibration. The results obtained the optimum combination of discrete element method (DEM) parameters for pregelatinized starch, Poisson's ratio 0.257, shear modulus 1×10⁹ Pa, granule-particle static friction coefficient 0.165, unit normal stiffness 2.419 2×10⁹ N·m^-3, unit tangential stiffness 7.954 6×10⁹ N·m^-3, and strength of adhesive force -0.009 155 8 N. For microcrystalline cellulose, Poisson's ratio 0.381, shear modulus 1.04×10⁹ Pa, particle-particle static friction coefficient 0.719, unit normal stiffness 3.171 5×10⁹ N·m^-3, unit tangential stiffness 6.746 2×10⁹ N·m^-3, and strength of adhesion -0.038 7 N. For optimum combinations of the DEM parameters for the binary blend of excipients, particle-particle collision recovery coefficient 0.1, unit normal stiffness 9.947 1×10⁹ N·m^-3, unit tangential stiffness 1.994 5×10⁹ N·m^-3, and adhesion force strength -0.060 35. The simulation results under the optimal parameter combination are similar to the experimental results, indicating that the calibrated parameters can be used for discrete element simulation research and provide theoretical basis and data support for the subsequent intelligent and continuous production of tablets.