To find out whether cantharidin inhibited osteosarcoma progression via down-regulating miR-214-3p expression was achieved by specifically targeting the DKK3 expression, thus to decrease β-catenin nuclear translocation and cause an reduced Wnt/β-catenin signaling activity in osteosarcoma cells, we firstly investigated outcome of cantharidin on DKK3/GSK-3β/Wnt/β-catenin signaling. The gene discussed is DKK3; the disease is osteosarcoma.