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Objective To observe the inhibitory effects of human fetal dermal mesenchymal stem cells (FDMSCs) on proliferation, migration, and invasion of human melanoma cells (A375 cells). Methods FDMSCs were extracted by en zyme digestion method from the back skin of healthy fetuses at 16-20 weeks of gestation and identified. A375 cells were se lected and divided into three groups. FDMSCs conditional medium was added to the F-CM group, adult dermal fibroblasts conditional medium was added to the A-CM group, and DMEM low-glycemic blank medium was added to the Control group. CCK-8 cell proliferation assay, wound healing assay and cell invasion assay were used to measure the relative cell vitality, cell migration rate and the number of invasive cells in each group. Results FDMSCs could be successfully extracted from human fetal skin with positive expression of MSCs specific markers like CD44, CD90, CD105 and embryonic specific markers like SSEA-4 and OCT-4. Furthermore, FDMSCs had the ability of multidirectional differentiation into lipid, bone and cartilage. Compared with Control group, the relative cell viability, cell mobility and the number of invasive cells in the F-CM group decreased (all P<0. 05). Conclusion FDMSCs can inhibit proliferation, migration, and invasion of A375 cells. [ABSTRACT FROM AUTHOR]