Metastasis is a major cause of death of patients with malignant tumors. Matrix metalloproteinases (MMPs) are important for the migration and invasion of various types of cancer cell. Propofol is a known anesthetic agent, widely used for short-term anesthesia and for longer-term sedation. Propofol inhibits the proliferation of a variety of tumor cells, but there is no available information regarding propofol-inhibited migration and invasion of tumor cells in vitro. In this study, we investigated the effects of propofol on the migration and invasion of human lung carcinoma A549 cells. Wound healing assay and Boyden chamber assays indicated that propofol inhibited the migration and invasion of A549 cells in vitro. Gelatin zymographic analysis showed the inhibitory effect of propofol on the activation of expression MMP-2. Western blot analysis also indicated that propofol suppressed the protein expiration of growth factor receptor-bound protein 2 (GRB2), Jun N-terminal kinases 1/2 (p-JNK1/2), p-p38, MMP-2 and MMP-9 in A549 cells. Results from real-time PCR assay also showed that propofol inhibited the mRNA gene expression of MMP-2, -7 and -9, and enhanced that of tissue inhibitor of metalloproteinase 1 (TIMP1) and TIMP2 in A549 cells. Taken together, these data show that propofol inhibits MMP-2 and -9 mRNA and protein expressions, resulting in suppression of lung cancer cell invasion and migration in vitro.