The Hedgehog (Hh) signalling pathway is involved in cell differentiation, growth and tissue polarity. This pathway isalso involved in the progression and invasion of various human cancers. Osteosarcoma, a subtype of bone cancer, iscommonly seen in children and adolescents. Typically, pulmonary osteosarcoma metastases are especially difficult tocontrol. In the present paper, we summarise recent studies on the regulation of osteosarcoma progression andmetastasis by downregulating Hh signalling. We also summarise the crosstalk between the Hh pathway and othercancer-related pathways in the tumourigenesis of various cancers. We further summarise and highlight the therapeuticvalue of potential inhibitors of Hh signalling in the clinical therapy of human cancers.