In the present study, the major findings were that vanillin: (i) decreases HIF-1α protein levels and that this effect is independent of proteasomal degradation; (ii) suppresses STAT3 phosphorylation and its promoter occupancy on the proximal region of HIF-1α; and (iii) attenuates cell migration by down-regulating HIF-1α target genes associated with cancer metastasis in A375 and A2058 human malignant melanoma cells. This evidence concerns the gene STAT3 and cancer.