Abstract: Fretting wear is the main cause of loosening between the artificial joint biological fixing material and the bone tissue. Through simulating the tangential fretting behavior in vitro, the fretting wear mechanism between two biological fixing materials (titanium-bead coating and hydroxyapatite coating) and cortical bone interface was explored. The lubrication condition was 25% calf serum to simulate the joint lubrication in the human body. A self-made multifunctional friction and wear testing machine was used to carry out the tangential fretting friction and wear experiment. By changing the fretting load and amplitude, it simulated the different tangential fretting state of the implant and bone interface in the daily life of the human body in vitro. The surface morphology and surface profile after wear were observed and analyzed. The influence of different parameters on the fretting wear of the fixed interface was studied, and the mechanism of the fretting wear of the interface was explored. The relationship between fretting, loose and bone injury of biological fixation interface was established. The results showed that under large displacement amplitude and small normal load, the interface was in the gross slip zone, which was dominated by abrasive wear. There were a lot of cracks and wear debris on the surface of the cortical bone, and the fixed interface was easy to loosen, which was not conducive to biological fixation. When the normal load and the small displacement amplitude were larger, the interface was in the partial slip zone, and the elastic-plastic coordination between the interfaces was dominant. In the partial slip zone, the friction interface was stable, and the corresponding working condition was the non-slip zone. The main wear mechanism was spalling. It was advantageous for the artificial joint biological fixation interface. As the amplitude of the fretting displacement increased, the interface friction coefficient increased, and the damage of cortical bone increased. As the normal load increased, the interface friction coefficient decreased. The interface sliding between the titanium bead coating and the cortical bone need to overcome the frictional resistance between the friction pair interface and the resistance caused by the relatively rough interface of the two interfaces. The interface friction coefficient between the titanium bead coating and the cortical bone was greater than 1, and it was relatively stable. The fixation effect of the titanium bead coating and the cortical bone was better. The relationship between the loosening and fretting parameters of the titanium bead coating and HA coating and the biological fixation interface of the bone tissue was explored, and the working condition boundary of the partial slip zone was divided. The optimal parameters of the interface between the titanium bead coating and the cortical bone were the normal load of 5 N and the displacement amplitude of 50 μm. The optimal parameters of the interface between HA coating and cortical bone were the normal load of 10 N and the displacement amplitude of 50 μm. The relationship between fretting-loosening-bone damage was established. By comparing the friction and wear mechanism of the two materials, it was found that the interface fixation effect between titanium bead coating and cortical bone was better, and the interface damage between hydroxyapatite coating and cortical bone was smaller. The results play a certain reference role for the biological fixation of artificial joints.