Objective To design customized titanium alloy lunate prosthesis, construct three-dimensional finite element model of wrist joint before and after replacement by finite element analysis, and observe the biomechanical changes of wrist joint after replacement, providing biomechanical basis for clinical application of prosthesis. Methods One fresh frozen human forearm was collected, and the maximum range of motions in flexion, extension, ulnar deviation, and radialis deviation tested by cortex motion capture system were 48.42°, 38.04°, 35.68°, and 26.41°, respectively. The wrist joint data was obtained by CT scan and imported into Mimics21.0 software and Magics21.0 software to construct a wrist joint three-dimensional model and design customized titanium alloy lunate prosthesis. Then Geomagic Studio 2017 software and Solidworks 2017 software were used to construct the three-dimensional finite element models of a normal wrist joint (normal model) and a wrist joint with lunate prosthesis after replacement (replacement model). The stress distribution and deformation of the wrist joint before and after replacement were analyzed for flexion at and 15°, 30°, 48.42°, extension at 15°, 30°, and 38.04°, ulnar deviation at 10°, 20°, and 35.68°, and radial deviation at 5°, 15°, and 26.41° by the ANSYS 17.0 finite element analysis software. And the stress distribution of lunate bone and lunate prosthesis were also observed. Results The three-dimensional finite element models of wrist joint before and after replacement were successfully constructed. At different range of motion of flexion, extension, ulnar deviation, and radial deviation, there were some differences in the number of nodes and units in the grid models. In the four directions of flexion, extension, ulnar deviation, and radial deviation, the maximum deformation of wrist joint in normal model and replacement model occurred in the radial side, and the values increased gradually with the increase of the range of motion. The maximum stress of the wrist joint increased gradually with the increase of the range of motion, and at maximum range of motion, the stress was concentrated on the proximal radius, showing an overall trend of moving from the radial wrist to the proximal radius. The maximum stress of normal lunate bone increased gradually with the increase of range of motion in different directions, and the stress position also changed. The maximum stress of lunate prosthesis was concentrated on the ulnar side of the prosthesis, which increased gradually with the increase of the range of motion in flexion, and decreased gradually with the increase of the range of motion in extension, ulnar deviation, and radialis deviation. The stress on prosthesis increased significantly when compared with that on normal lunate bone. Conclusion The customized titanium alloy lunate prosthesis does not change the wrist joint load transfer mode, which provided data support for the clinical application of the prosthesis.