In this work, a novel series of aminoisoquinolinylamide derivatives 1a-c and 2a-f were synthesized via several reaction steps, starting from 2-methyl-4-nitrobenzonitrile (3) and 1-chloro-5-nitroquinoline (8). And their antiproliferative activities were screened against A375 human melanoma cell line compared to Sorafenib as a reference compound. Among them, compound 1b and 1c exhibited meaningful inhibitory activities. These results demonstrated that aminoisoquinolinylamide scaffold possesses the possibility as the treatment for melanoma.