CD147, a leukocyte surface molecule over-expressed in T-lymphoma cells, is reportedly associated with lymphocyte activation and proteinase production via interactions with fibroblasts and plays a role in stromal invasion by lymphoma cells. To determine the role of CD147 in the progression of T-lymphoma, we performed siRNA interference-mediated knockdown of CD147 in a CD147-expressing Jurkat T-cell line. CD147 knockdown resulted in the decreased proliferation and migration of Jurkat cells and reduced the adhesion of Jurkat cells to extracelluar matrix fibronectin in vitro. CD147-siRNA inhibited the activation of Jurkat cells via down-regulation of CD25 expression. Our results indicate that CD147 is involved in T-lymphoma progression, a finding useful in efforts to develop targeted therapies to treat patients with T-lymphoma.