Nuclear Pore Complexes (NPCs) are involved in the regulation of nucleo-cytoplasmic trafficking. Drosophila Nup154 encodes a nucleoporin component of the NPC that is expressed in high proliferating tissues such as germ cells. Hypomorphic mutations in this gene cause male and female sterility and reduction of cell proliferation in the adult fly. Here, we present evidences of a decrease in the number of spermatogonial cells in Nup154 mutants, caused both by increased cell death and reduced cell proliferation. Furthermore, we also found that RNAi-mediated depletion of Nup154 in cultured cells prevented nuclear accumulation of the transcription factor Mothers against Dpp (Mad), suggesting a possible regulatory role for Nup154 in TGF-β signal transduction. These results were confirmed in vivo on mutant testes where we observed a similar defect in the nuclear accumulation of the co-Smad Medea.