Osteosarcoma (OS) patients with metastasis have very dismal prognoses, and lack effective target therapies. Overexpression of cytosolic phospholipase A2 (cPLA 2) has been shown to promote progression in several types of cancers, but its functions in OS have not been investigated. In our study, the expression of cPLA 2 a was detected with immunohistochemistry in 102 cases of OS. The clinical significance of cPLA 2 a was evaluated by analyzing its correlation with clinicopathological factors. The prognostic significance of cPLA 2 a was estimated by univariate and multivariate analysis. The oncogenic functions of cPLA 2 a on cell proliferation and invasion were investigated by MTT assay and tranwell assay respectively. Western blotting was applied to detect the markers of epithelial-mesenchymal transition (EMT) after silencing cPLA 2 a expression or inhibiting its activity by a specific antagonist. In our study, high expression of cPLA 2 a was significantly associated with metastasis and advanced Enneking stage. High cPLA 2 a expression was significantly associated with poor prognosis and it was an independent prognostic biomarker of OS. By silencing cPLA 2 a or inhibiting its activity by a specific antagonist, we demonstrated that cPLA 2 a promoted cell invasion of OS cells via inducing the EMT process. High cPLA 2 a expression was an independent prognostic biomarker of OS, and cPLA 2 a could promote OS cell invasion via inducing the EMT process, indicating that cPLA 2 a was an independent prognostic biomarker and may be an effective drug target for OS. [ABSTRACT FROM AUTHOR]