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The role of hematopoietic hedgehog signaling in MPN remains incompletely understood despite data suggesting Hh pathway inhibitors have therapeutic activity in patients. We aim to systematically interrogate the role of canonical vs. non canonical Hh signaling in MPN. We show that Gli1 protein levels in patient PBMCs mark fibrotic progression and that in murine MPN models, absence of hematopoietic Gli1, but not Gli2or Smo, significantly reduces MPN phenotype and fibrosis, indicating that GLI1 in the MPN clone can be activated in a non-canonical fashion. Additionally, we establish that hematopoietic Gli1has a significant effect on stromal cells, mediated through a druggable MIF/CD74 axis. These data highlight the complex interplay between alterations in the MPN clone and activation of stromal cells and indicate Gli1represents a promising therapeutic target in MPN, particularly Hh signaling is dispensable for normal hematopoiesis.