Abstract: In order to prevent the highly uneven, eccentric wear of the subsea wellhead casing hanger and its connecting nipple during the operation of semi-submersible rig, and to further ensure the integrity of oil and gas wells, research was conducted and a preventative technology of subsea wellhead casing hanger eccentric wear is proposed in this paper. Taking high temperature high pressure (HTHP) offshore exploration well M as an example, the ϕ273.1 mm casing hanger and its connecting nipple experienced severe eccentric wear and the residual casing thickness failed to meet the integrity requirements. The following factors can cause eccentric wear of casing hanger: as the sea conditions during operation, the degree of drilling rig deviating from wellhead, whether the flexible joint of riser is twisted, the inner diameter of casing hanger. All factors were studied. Then, combined with the calculation results of finite element software, this paper proposes preventive measures of accurately monitoring the deviation of rig from the wellhead to correct the eccentric wear in time, and selecting the wear bushing of casing hanger with the same inner diameter as the casing. During well filling/sidetracking of well M and the subsequent drilling, workover and abandonment in 11 wells, preventive measures were adopted during operations of the four semi-submersible rigs and the casing hangers and connecting nipples didn’t experience significant eccentric wear. Field applications showed that the prevention technologies could effectively protect the subsea wellhead hanger and ensure the integrity of oil and gas wells. Thus this study showed the potential for wide application and adoption.