Tumor tropism is an important property of mesenchymal stem cells (MSCs) that has been used in tumor‑targeting therapies. However, the effects of MSCs on tumors remain controversial. The aim of the present study was to investigate the effects of MSCs on A375 melanoma cells. Umbilical cord‑derived mesenchymal stem cells (UCMSCs) were co‑cultured with A375 cells. MTT and Transwell assays were used to assess cell proliferation and invasion, while flow cytometry was performed to detect the apoptosis and the cell cycle distribution of A375 cells. The expression levels of kinases were assayed by western blotting and fluorescence analysis was conducted to detect cytoskeletal rearrangement. The results clearly indicated that UCMSCs could inhibit the proliferation, induce apoptosis and suppress the invasion of A375 cells. Mechanistic studies revealed decreased expression of several kinases (AKT, STAT3 and mTOR) and UCMSCs were also found to promote cytoskeletal rearrangement in A375 cells. These results confirmed that UCMSCs exert antitumor effects on melanoma A375 cells.