BackgroundZerumbone (ZER) is a phytochemical that appears to regulate cell proliferation and apoptosis. It has been reported to have an anti-tumour effect in various malignant cells; however, the effect and the mechanism of ZER on melanoma cells needs to be clarified. AimTo explore whether ZER has an effect on human melanoma cells and to identify the mechanisms involved. MethodsWe determined the chemotherapeutic action of ZER on the human malignant melanoma (MM) A375 cell line by CCK-8 immunohistochemistry, Hoechst 33342 staining and flow cytometry analysis. We also investigated the signalling pathways by which ZER induces apoptosis in A375 cells, using western blotting, reverse transcription PCR and caspase-3 activity analysis. ResultsZER induced significant cytotoxic action in A375 cells. Hoechst 33342 staining and flow cytometry apoptosis analysis further demonstrated that ZER induced apoptosis in A375 cells. Treatment with ZER downregulated Bcl-2 gene and protein levels, upregulated Bax and Cytochrome c gene and protein levels, and activated Caspase-3. ConclusionsZER might have a chemotherapeutic effect on human melanoma cells through mitochondria-mediated pathways.