In the present study, we for the first time found that the expression levels of S100A4 protein were correlated positively with activity of Shh-Gli1 signals in pancreatic cancer tissues and the Gli1 protein upregulated S100A4 mRNA through cis-activation manner in PC cells which established an exact molecular pathway from Shh-Gli1 signals to S100A4 in PC cells. This evidence concerns the gene GLI1 and pancreatic neoplasm.