Autocrine motility factor (AMF) acts as a growth inhibitor as well as activator of proliferating cancer cells. This study demonstrated that AMF significantly inhibited melanoma cells by downregulation of the mRNA and protein expression of glucose-6-phosphate dehydrogenase (G6PD) and hypoxia-inducible factor (HIF-1α). Moreover, the synergy between activities of AMF and cytotoxic octyl gallate (OG) was observed.