Trephination is one of the basic operations of keratoplasty, and the biomechanical mechanism of the operation can be revealed based on three-dimensional modeling and simulation of trephine cutting cornea. Methods: Based on the analysis of the physical and biomechanical characteristics of corneal trephination, a three-dimensional numerical model of corneal trephination is built, where the cornea can be simplified to two layers structure including stroma and epithelium, and the trephine cuts the cornea under the vertical motion load and the rotational motion load. A three-dimensional failure criterion of corneal material is proposed based on the yield strength theory. On this basis, trephination simulation is carried out, and the units of corneal material are removed from the model when they meet the defined failure criterion. Results: Under the given parameters including the velocity, the angle and the angular velocity, the trephine force curves, include the linear cutting force and the rotary cutting force are obtained, and show the change of the forces with displacement during the process of trephination simulation. The maps of the equivalent stress show the destruction and deformation of the cornea. Then, the experiment of robotic trephination is carried out under the same parameters and the effectiveness of the simulation is evaluated. Conclusions: Based on mechanics theory and finite element method, the process of trephine cutting cornea has been reproduced, and the interaction mechanism is revealed, which lays the foundation for the development of real-time simulation and virtual system of the corneal surgery.