Objective:To investigate the effect of liquiritigenin (LQ) on cell migration and invasion by monitoring regulation of miRNA and its downstream target gene expression in human melanoma A375 cells. Methods:MTT assay was used to detect the cell viability of A375 cells treated with different concentrations of LQ. The effect of LQ on cells migration and invasion was measured by wound healing method and Transwell migration/invasion assay. Decreased expression of hsa-miR-4487 and hsa-miR-4534 was screened by miRNA Expression Array,and confirmed by quantitative PCR. The expression levels of PTEN,p-AKT,AKT,MMP2,and TIMP2 were examined by Western blot. Results:Ten to 100 μmol/L of LQ treatment on A375 cells for 24 h had no obvious damage to cells. LQ inhibited cell migration and invasion in a dose-dependent manner. Hsa-miR-4534 and hsa-miR-4487 expression were downregulated by LQ. Meanwhile,LQ increased the expression level of PTEN and TIMP2,and decreased p-AKT and MMP2 expression in A375 cells. Conclusion:LQ inhibits migration and invasion of A375 cells,probably via regulating miRNA expression and its downstream target genes.