Overexpression of ZEB1 relates to metastasis and invasion in osteosarcoma. This study aimed to investigate the expression of ZEB1 in osteosarcoma tissues and to discuss the relationship between ZEB1 expression and osteosarcoma metastasis.Using RT-PCR and Western blotting, the mRNA and protein expressions of ZEB1 in the osteosarcoma and normal bone tissues were detected. Using the RNA interference technique, the expression of ZEB1 in the human osteosarcoma MG-63 cell line was downregulated, and the changes in the invasion of MG-63 cells were examined.The positive mRNA expression rate of ZEB1 in the osteosarcoma tissues was significantly higher than that in normal bone tissue (P < 0.05). The protein expression level of ZEB1 in the sarcoma tissues from patients with positive lung metastasis was significantly higher than that from patients without lung metastasis (P < 0.05). After the transfection of ZEB1 siRNA into the MG-63 cells, the protein expression of ZEB1 was significantly reduced (P < 0.05), and the number of cells that passed through the Transwell chamber was significantly lower than that in the non-transfected control group as well as the transfected control group (P < 0.05).The overexpression of ZEB1 in osteosarcoma may be related to the carcinogenesis and development as well as metastasis and invasion of osteosarcoma.Copyright © 2011 Wiley Periodicals, Inc.