Abstract: The hedgehog (HH) signaling pathway plays an important role in the growth and metastasis of tumor cells, in addition to its role in the development of the embryo and the regeneration and repair of tissues in adults. Aberrant activation of this pathway has been found to be involved in the invasion and progression of several malignant human tumors. The Gli transcription factors that directly regulate the transcription of targeted genes act at the end of the Hh signaling cascade, and play an important role in carcinogenesis. Gli has also been found to interact with other signaling pathways commonly activated in human cancers; as such, the targeted inhibition of Gli-mediated transcription is likely valuable during the development of novel agents. The focus of this review is to summarize a number of the known mechanisms of HH - Gli signaling in tumor development. The review also aims to discuss its emerging role in cancer, the transcriptional activity and the carcinogenesis of Gli, major advances in the role of Gli in the HH signaling pathway, and its prospects in clinical applications.