Given that HIF-1α upregulation is frequently implicated in response to hypoxic stress and autophagic process, the present study showed that α-MSH significantly increased HIF-1α transcriptional activity and both protein and mRNA levels in B16-F10 melanoma cells during hypoxia, and HIF-1α-mediated Bcl-2 family genes (BNIP3 and BNIP3L) were also elevated by double stresses (α-MSH and hypoxia). Here, BNIP3 is linked to melanoma.