Melanoma is the most serious type of skin cancer as a malignant tumor of melanocytes. In this work, the syntheses of a novel series of benzaminoquinoline derivatives 1a-c and their antiproliferative activities against A375 human melanoma cell line were described. All the compounds (IC50=0.78-1.02μM) showed superior antiproliferative activities to Sorafenib (IC50=5.58μM) as a reference compound. These results suggested that benzaminoquinoline derivatives have potentials as a therapeutic agent for the treatment for melanoma.