It has been reported that zerumbone (ZER) has marked effects on the regulation of cell proliferation and migration in multiple types of cancer, and has anti-cancer effects on various types of malignant cell. However, the effects and underlying molecular mechanisms of treatment with ZER on melanoma cells remain unclear. In the present study, the effect of treatment with ZER on the proliferation, migration and mitochondrial function of the human melanoma cell line CHL-1 was investigated. The results of the present study indicated that treatment with ZER significantly inhibited CHL-1 cell proliferation (P<0.001). Cell migration analysis further demonstrated that ZER inhibited the migration of CHL-1 cells (P<0.001). Treatment with ZER significantly increased cellular reactive oxygen species levels (P<0.001), reduced matrix membrane potential (P<0.001), decreased ATP (P<0.001) and mitochondrial DNA (P<0.001) levels, and decreased mitochondrial transcription factor A mRNA levels (P=0.002). The results of the present study suggested that the inhibition of proliferation and migration was mediated by altered mitochondrial function. In conclusion, the results of the present study suggested that ZER has chemotherapeutic effects on human melanoma cells by altering mitochondrial function.