Hedgehog (Hh) signaling and the pyruvate kinase isoenzyme M2 (PKM2 or M2-PK) are often involved in tumorigenesis and growth. Aberrant activation of Hh signaling is found in a variety of malignancies. In tumor cells, PKM2 determines whether glucose is used for the synthesis of cellular building blocks or the production of lactate for energy regeneration; it associated with the Warburg effect. Gli1 is a downstream molecule of the Hh signaling pathway; however, the association between Hh signaling and PKM2 is not well understood. In the present study, it was identified that PKM2 and Gli1 expression levels were significantly elevated in hepatocellular carcinoma (HCC) compared with para-carcinoma. In vitro study revealed that overexpression of PKM2 in HepG2 cells upregulated the transcription of Gli1, while the ablation of PKM2 by shRNA caused the downregulation of Gli1 gene expression. Gli1 transcription could be rescued by PKM2. Overall, these findings suggest that PKM2 is a regulator of Gli1 gene expression in HCC, and may contribute to tumorigenesis through Gli1.