Visfatin is considered to be a biomarker in various types of cancers. However, no evidence has been reported for the direct effect of visfatin on osteosarcoma cell metastasis. The aims of the present study were to investigate the influence of visfatin on the migration and invasion of osteosarcoma cells and clarify the underlying mechanism. The expression levels of epithelial-mesenchymal transition (EMT) markers, as well as the transcriptional factor Snail-1, were first detected at both the protein and mRNA levels in U2OS osteosarcoma cells after stimulation of visfatin. Then the expression of NF-κB (p65) was detected by western blot analysis, and siRNA of Snail-1 and inhibitor of NF-κB were used to investigate the effect of visfatin. Finally, migration and invasion of the cells were detected respectively by scratch wound healing and transwell assays. Visfatin downregulated E-cadherin and upregulated N-cadherin in concentration- and time-dependent manners at the protein and mRNA levels. The expression of Snail-1 was also upregulated. Moreover, visfatin also promoted the nuclear translocation of the NF-κB pathway. Administration of siRNA of Snail-1 and the inhibitor BAY11-7082 validated the roles of Snail-1 and NF-κB in the visfatin-induced regulation of EMT markers. Migration and invasion of U2OS osteosarcoma cells were promoted following the application of visfatin. These results demonstrated that visfatin enhances the migration and invasion of osteosarcoma cells via the NF-κB/Snail-1/EMT pathway.