CAF-derived exosomes, rich in SHH, increased the expression of PTCH1, SMO, and GLI1 in ESCC cells, indicating activation of the SHH signaling pathway, resulting in enhanced migratory and proliferative abilities of ESCC cells. CAF-derived exosomes increased tumor weight and volume in vivo, this effect could be reversed by cyclopamine. This evidence concerns the gene SHH and esophageal squamous cell carcinoma.