In this study, we examined the inhibitory effects of lupeol, an extract of Euphorbia fischerana Steud, on human breast cancer MDA-MB-231 cells migration and invasion. Lupeol was found to inhibit the invasion of MDA-MB-231 in the cell adhesion assay, transwell test and wound healing assay. The expression of cyclooxygenase-2 (COX-2), matrix metalloproteinase-2 (MMP-2), -9 (MMP-9) and nuclear transcription factor-kappa B (NF-κB) p65 in breast cancer following treatment with different concentrations of lupeol was analyzed with Western blot. Lupeol inhibited the migration and invasion of MDA-MB-231 cells in a dose- dependent manner in vitro (P < 0.05). The expression of COX-2, MMP-2, MMP-9 and NF-κB p65 levels was significantly down-regulated. These observations suggest that lupeol can inhibit the abilities of invasion of MDA-MB-231 cells by inhibiting the protein expression of COX-2, MMP-2 and MMP-9. Its mechanism may be related to inhibition of the nuclear NF-κB signal pathway.