Kruppel-like factor-6 (KLF6) is involved in differentiation, cell cycle control and proliferation in several cells. Klf6-/- knockoutmice die by embryonic day 12.5 and are characterized by reduced hematopoietic differentiation in yolk sacs and impaired placental development. KLF6 is expressed in human term placenta, however little is known about its expression during trophoblast differentiation and its role in transcription of placenta specific genes. qRT-PCR and western blot revealed an increase in KLF6 expression which preceded morphological differentiation of cytotrophoblasts and Jeg3 cells. KLF6 alone or in cooperation with Sp1, activated promoter constructs of Pregnancy-specific glycoproteins genes, which are biochemical markers of trophoblast differentiation. Overexpressed KLF6 had a clear nuclear signal, while endogenous KLF6 was localized to the nucleus but mainly to the cell cytoplasm suggesting association with cytoskeletal filaments. No substantial change in subcellular distribution profile was observed in trophoblast cells induced to differentiate or cultured in hyperglycemia conditions. In contrast, KLF6 pattern was clearly modified in Jeg3 cells undergoing mitosis. These data are in line with a putative role of KLF6 in differentiation, proliferation and transcriptional regulation of placenta specific genes in trophoblast. Supported by CONICET, FONCyT and SECyT-UNC.