Ti-based ceramic coatings on Ti6Al4V substrates were successfully prepared through a laser cladding process using pre-placed starting materials of TiCN + SiO2 mixed powder without or with adding a 3 wt % CeO2 nanoparticles additive, aiming at improving the wear resistance of the Ti6Al4V alloy for biological applications. The effects of the CeO2 nanoparticles additive on the microstructure, microhardness, and wear performance of the coatings were analyzed in detail. The observations showed that the main compositions of the cladding coating were TiCN and TiN phase. Compared to the coatings without CeO2, the coatings modified with CeO2 nanoparticles led to more excellent mechanical properties. The average microhardness of the coatings modified with CeO2 nanoparticles was approximately 1230 HV0.2, and the wear volume loss of the coatings modified with CeO2 nanoparticles was approximately 14% less than that of the coatings without CeO2 under a simulated body fluid (SBF) lubrication environment. The major reasons included that the microstructure of the coatings modified with CeO2 nanoparticles was refined and compact granular crystalline. The wear mechanisms of the coatings were investigated from the worn surface of the coatings, wear debris, and the worn surface of the counter-body balls. The wear mechanisms of the coatings without CeO2 included abrasive wear, adhesive wear, and fatigue wear, while the wear mechanisms of the coatings modified with CeO2 nanoparticles included only abrasive wear and adhesive wear, because the fine microstructure of the coatings had an excellent resistance to fatigue wear.