In this study, after micro-arc oxidation, anodic oxidation and laser cladding on the surface of Ti-6Al-4V-0.5Ni-0.5Nb alloy used for drill pipe, the microstructure and structural characteristics of the substrate and treated surfaces were investigated and compared. Wear experiments were carried out on all the samples with GCr15 and SiC grinding materials under different applied load, and the friction characteristics and wear morphology were analyzed. It can be revealed that the laser cladding coating was denser, non-porous and thicker than that of the other two oxidation layers. The COF of the alloys treated by three surface treatments were significantly reduced compared with that without treatment, the mass loss and wear rate of the laser cladding coating were the lowest. Compared with two oxidation treatments, the laser cladding treatment can significantly increase the hardness, thickness and wear resistance of the alloy surface due to the WC, W2C and η-Co phases contained in the laser cladding coating, and change the wear mechanism of Ti-6Al-4V-0.5Ni-0.5Nb alloy from severe abrasive and adhesive wear to mild abrasive wear because of the metallurgical bonding between the laser cladding coating and the substrate. In conclusion, the wear resistance of Ti-6Al-4V-0.5Ni-0.5Nb alloy drill pipe can be significantly improved by laser cladding treatments to meet the needs of rigorous HTHP drilling condition.