CD44 is a cell-surface receptor for hyaluronic acid and also interacts with other ligands, such as osteopontin, collagens, and matrix metalloproteinases. A large number of CD44 isoforms can be generated by the insertion of different combinations of at least nine exons. Increased CD44 antigen is associated with relapses in non-small cell lung cancers. Furthermore, an increasing quantity of evidence suggests that CD44 has various functions related to inflammatory disease. CD44 deficiency induces severe liver injury. CD44-hyaluronate mediates in lymphocyte T and monocyte adhesion to the endothelium, stimulates proinflammatory cytokine release from macrophages and participates in dedifferentiation phenotype of smooth muscle cells from contractile state to synthetic one.