Background and Aims: Normal cells become tumorigenic owing to mutations in oncogenes and tumor suppressor genes modulating cell division. Cancer cells break down extracellular matrix to metastasize other tissues. Therefore, the development of natural and synthetic substances that suppress metastatic enzymes such as matrix metalloproteinase (MMP)-2 and MMP-9 is useful to inhibit metastasis. Silibinin is the main ingredient of silymarin extracted from the seeds of milk thistle plants having lung cancer-suppressing effects and liver protection. The purpose of this study was to investigate the inhibitory effect of silibinin on the invasion of human fibrosarcoma cells. Methods: The effect of silibinin on cell viability was measured in HT1080 cells using an MTT assay. The MMP-9 and MMP-2 activities were analyzed using a zymography assay. The expression of proteins in cytoplasm related to metastasis was examined by western blot analysis and immunofluorescence assay. Results: In this study, silibinin above 20 \muM showed growth inhibitory effects. Silibinin above 20 \muM remarkably inhibited the levels of MMP-2 and MMP-9 activation under phorbol myristate acetate (PMA) treatment conditions. Furthermore, silibinin at 25 \muM reduced the levels of MMP-2, IL-1\beta, ERK-1/2, and p-p38 expression and silibinin above 10 \muM inhibited cell invasion on HT1080 cells. Conclusions: These findings indicate that silibinin may have an inhibitory effect on the enzymes involved in invasion, hence it might influence the metastatic ability of tumor cells.