The Drosophila gene hindsight (hnt), homologue of mammalian Ras responsive element binding protein-1 (RREB-1), encodes a C2H2-type Zinc finger nuclear protein that is required for several developmental processes including germ band retraction, tracheal differentiation, retinal morphogenesis, and proper growth of the follicular epithelium of the ovary. In some processes hnt has been identified as a direct target of the Notch signaling pathway. Given the importance of Notch signalling in the regulation of the adult intestinal stem cells (ISCs), we have investigated the regulation and function of hnt in this context. We show that hnt is expressed throughout the larval and adult midgut, and we further demonstrate that Hnt is required for ISC establishment during the larval/pupal transition. In the adult midgut we find that ISC hnt expression does not require Notch signalling, but is dependent on the EGFR/RAS/MAPK signalling pathway. Moreover, we find Hnt overexpression to be a potent effector of ISC loss through enterocyte (EC) differentiation. We also show that EC differentiation via Hnt overexpression can suppress ISC tumour formation associated with either the loss of Notch signalling or the activation of the EGFR/RAS/MAPK signalling pathway.