Kisspeptin (KiSS-1) gene, initially described as a melanoma metastasis suppressor gene, encodes a number of peptides (kp-54, kp-14, kp-13, kp-10), which are endogenous ligands to a G protein-coupled receptor, referred as hOT7T175 or AXOR12 or GPR54. So far intensive investigation has provided substantiate evidence supporting the role of KiSS-1/GPR54 system in cancer biology as well as in the regulation of the reproductive function and trophoblast invasion. The precise mechanism by which KiSS-1/GPR54 system is affecting cancer cell growth and metastasis includes complex endocrine, paracrine and autocrine actions. Nevertheless, the detail mechanism of such actions is still under intensive investigation. Herein we review the evidence which support the role of KiSS-1/GPR54 system in cancer biology.