Abstract: Tetraspanins are a family of small cell surface proteins characterized by four highly conserved transmembrane domains, which are thought to be involved in the regulation of a broad range of functions, including cell growth, conglutination, and migration. The tetraspanin superfamily ( TM4SF ) may be associated with other cell surface proteins such as tetraspanins, integrin growth factor and its receptor, the HLA family, and MHCs. They form the tetraspanin web wherein tetraspanins form the cores. The tetraspanin web indirectly or directly affects conglutination, differentiation, migration, and metastasis of the cancer cell by signal pathway. Current research studies show that CD151, CD82, Tspan8, and Tspan1 are closely associated with liver cancer, which may affect the progress of liver cancer by regulating conglutination, migration, and metastasis of liver cancer cells. KAI1/CD82 is a tumor suppressor gene that inhibits the migration and metastasis of liver cancer cell by upregulating the level of its expression. CD151 is expressed widely in liver cancer, which shows the possible use of CD151 overexpression and c-Met overexpression in predicting the progression of liver cancer, and CD151 may be potential molecular therapeutic targets for liver cancer. The progression and the prognosis of liver cancer can be predicted using Tspan8 ( CO-029 ) and Tspan1 ( NET-1 ).