Objective(s): The study aimed to uncover the underlying mechanism linking wear particles to osteoclast differentiation, and we explored the effect of titanium particles of different sizes on CD147 expression and autophagy in macrophages. Materials and Methods: Effects of titanium particles on CD147 and RANKL mRNA were detected by QPCR; protein level of CD147 and Beclin-1 were detected by Western blot; soluble RANKL were detected by ELISA. To determine the effect of CD147 and autophagy, KG-1a cells were transfected with siRNA-CD147 or treated with autophagy inhibitor CQ (chloroquine), and then co-cultured with different sizes of titanium particles. Results: Our results showed that 0. 2-1. 2 μ m and 1. 2-10 μ m titanium particles up-regulate CD147 to activate autophagy, which increase the level of soluble RANKL to promote osteoclastogenesis. Suppression of CD147 with siRNA could diminish particle-induced autophagy and soluble RANKL expression. In addition, CQ could dramatically reduce particle-induced soluble RANKL expression. Conclusion: Our findings suggested a possible mechanism underlying wear debris-induced osteolysis and identified CD147 as a potential therapeutic target in aseptic loosening.