〔Abstract〕 Objective To investigate the expression of milk fat globule epidermal growth factor 8 protein(MFGE8) in osteosarcoma cell lines and its effects on the proliferation, apoptosis, invasion and migration ability of osteosarcoma cells(U2 OS). Methods The expression of MFGE8 protein in normal osteoblasts and osteosarcoma cell lines was examined by Western blot method. The relationship between MFGE8 mRNA expression and prognosis of osteosarcoma patients was analyzed by GEO database. The effects of down-regulation of MFGE8 on proliferation, apoptosis, migration and invasion of U2 OS cells were examined. Results Western blot method showed that the expression of MFGE8 protein was higher in osteosarcoma cells than that in normal osteoblasts and its was negatively correlated with the prognosis of osteosarcoma patients(allP<0.05); compared with sh-Ctrl(U2 OS cells transfected with the null group) group, the U2 OS cells in sh-MFGE8(U2 OS cells transfected with sh-MFGE8) group had decreased healing rate and invasion number while increased proliferation inhibition rate and apoptosis rate, and all differences were statistically significant(P<0.05). Conclusion MFGE8 is highly expressed in U2 OS of osteosarcoma cells, and down-regulation of MFGE8 can inhibit the proliferation, invasion and migration of U2 OS and induce their apoptosis.