Previous work indicates that matrix metalloproteinase-1 (MMP-1) gene expression is a prognostic factor for local recurrence and metastasis in human chondrosarcoma. The current study evaluates the effects of MMP-1 knock-down via RNA interference on chondrosarcoma metastasis in vitro. Of nine siRNA oligos tested, one showed a 90% inhibitory effect on MMP-1 gene expression. Stable attenuation of MMP-1 in chondrosarcoma cells was achieved by using a plasmid vector-based siRNA system. Pronounced MMP-1 activity suppression was accompanied by marked inhibition of tumor cell invasion. Cells in which MMP-1 has been stably silenced are useful tools to elucidate the mechanism of MMP-1 mediated tumor metastasis.