This work describes the function of two homeodomain proteins, HOP and NANOG, a family of protein previously known for their involvement in organogenesis and embryo patterning, in the context of gliomas, a tumor with a very poor prognosis. In addition, we address their possible interactions with the developmental and stemness signaling pathway Shh-Gli. We first describe the expression and function of HOP in the normal mouse hippocampus and in human gliomas. Our results suggest that HOP regulates hippocampal neural stem cells by negatively affecting cell survival. Moreover, HOP might acts as a tumor suppressor in gliomas by regulating apoptosis. In addition, we analyse interaction between HOP and the Shh-Gli pathway in gliomas/./ In a second part, we investigate the role of NANOG, a stemness homeodomain protein, in gliomas. We demonstrate that NANOG regulates proliferation, self-renewal and survival in glioma /in vitro/ and /in vivo /and we propose that NANOG can act downstream or in parallel of the Shh-Gli signalling. All together these data revealed new functions for homeodomain protein in tumoral processes that could lead to improvement of anti cancer treatments.