In the theory of traditional medicine, Gleditsia spina (GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. For these reasons, GS has been widely used as dermatologic agent clinically. The genetic profile for the effect of medicine on human derived melanoma cells of SK-MEL-2, was measured by using microarray technique, and the functional analysis on these genes was conducted. Total 253 genes were up-regulated and 439 genes down-regulated in cells treated with GS. Genes induced or suppressed by GS were all mainly concerned with metabolic process, regulation of biological process and protein binding. The network of total protein interactions was measured by using cytoscape program, and some key molecules that can be used for elucidation of therapeutical mechanism of medicine in future were identified. These results suggest the possibility of GS as anti-cancer drug and cosmetic agent, and also suggest that related mechanisms are involved in regulation of intra-cellular metabolism in melanoma cells.