Abstract: Objective:To investigate the relationship of Matrix Metalloproteinase-9 (MMP- 9) with human tumor invasion and/or metastasis. Methods:A double stranded RNA that targets the MMP- 9mRNA was transfected into HT 1080 cells and the cell biology was monitored. Results: MMP-9 interference depleted the corresponding mRNA and this MMP-9 extinction resulted in the following: ( 1) inhibited cell mobility; ( 2) increased cell adhesion; and ( 3) attenuated tumor cell migration. Addi -tionally, MMP- 9 knockdown concomitantly resulted in decreased levels of soluble ICAM-1, leading to adhesion defects and tumor metastasis. Moreover, an in vivo assay further demonstrated that MMP-9 interference affected the tumorigenesis of HT1080 cells in mice as follows: (1) inhibition of tumor growth; ( 2) reduced tumor volume; and ( 3) prolonged survival time. Conclusion:Overall, these observations define a novel critical role for MMP- 9 in the progression of HT1080 fibrosarcoma by changing the ICAM-1 from being in a membrane-anchored state to a solvable one which provides a promising lead for tumor therapy in clinics.