Since CD44 was found to be significantly inhibited in the human nasopharyngeal carcinoma cell line CNE-2L2 with profound reduction of malignant activities caused by inhibition of alpha-mannosidase Man2c1 gene expression and CD44 has been observed to be involved in many tumor-supporting functions, we studied the association of CD44 expression with the malignant activities of CNE-2L2 cells. Suppression of CD44 gene expression by RNA silencing technique resulted in profound reduction of malignant potential of the cells, including growth in vitro, colony formation, tumorigenesis and metastasis of tumors in nude mice. Direct injection of the adenoviruses harboring and producing siRNA to CD44 into the tumor inoculated with CNE-2L2 cells in nude mice caused inhibition of tumor growth. The data indicate a positive association of CD44 expression with the malignant activities of CNE-2L2 cells and suggest a possible therapeutic effect of direct introduction of siRNA to CD44 into tumors in some human solid tumors with high expression of CD44 gene.