Calycosin is an O-methylated isoflavone. It can be isolated from Astragalus membranaceus Bge. var. mongholicus and Trifolium pratense L. (red clover). Human melanoma cell A375 was chosen as study subject; The cell viability was determined by MTT assay after treated with calycosin,and the migration and invasion of A375 cells were measured by scratch test and transwell assay; qPCR was used to detect the expression levels of matrix metalloproteinase-2( MMP-2) and matrix metalloproteinase-9( MMP-9) in A375 cells. Calycosin could not inhibit A375 cell proliferation in the concentration range of 6. 25 ~ 100 μmol / L. Calycosin can inhibit A375 cell migration and invasion,and qPCR results confirmed that calycosin could inhibit the mRNA expression of MMP-2 and MMP-9.