Abstract: High-entropy alloys (HEAs), with their multi-principal element design, have emerged as a hot topic in materials science due to their distinct microstructures and superior mechanical properties.The crystal plasticity finite element method provides a powerful tool for analyzing the correlation between the microscopic deformation mechanisms and macroscopic mechanical behaviors of materials. In this study, by constructing a crystal plasticity finite element model coupled with grain size effects and developing a Vumat subroutine based on Abaqus, the regulatory mechanisms of microstructures on the strength-ductility synergy in CoCrFeNi-based HEAs are systematically revealed.The research findings show that the constructed crystal plasticity model for HEAs can accurately predict key indicators such as yield strength and ultimate strength. Further extending to the grain refinement strengthening of HEAs, it is found that with the increase in the volume fraction of the second phase, the yield strength and ultimate strength increase, while the uniform elongation (ductility) decreases. Based on 3D gradient microstructure modeling technology, this study innovatively confirms that when the grain size presents a linear gradient distribution, the material can achieve a better strength-ductility match. It further reveals that the gradient structure realizes strength-ductility synergy through stress partitioning (the fine-grained region bears high stress and the coarse-grained region accommodates deformation) rather than a simple mixing effect. Deformation twins participate in plastic distribution even at low strains and exhibit significant strengthening effects at high strains.The research results not only clarify the regulatory mechanisms of gradient structures and twins on the strength and ductility of HEAs but also supplement the action laws of size effects at the micro-nano scale, further enriching the correlation theory between the microstructure and macroscopic properties of HEAs.