Abstract: Objective To investigate the effect of propofol on cell invasion and expressions of aquaporin-3 (APQ-3) and matrix metalloproteinase-9 (MMP-9) in human lung adenocarcinoma cancer A549 cells. Method A549 cells were treated with propofol at the concentrations of 25, 50, and 100 μmol/L for 12 or 24 h. RT-PCR was used to detect the effect of propofol on AQP-3 mRNA level in A549 cells, and the effects of propofol treatments for 24 h on AQP-3 and MMP-9 protein expression and the invasive ability of A549 cells were assessed with Western blotting and Transwell assay, respectively. Results Compared with the control cells, the cells treated with 25, 50, and 100 μmol/L propofol showed a obvious inhibition of AQP-3 mRNA expression, with inhibition rates ranging from 0.19 to 0.65 in cells with a 12-h treatment and from 0.13 to 0.41 in cells treated for 24 h; 100 μmol/L propofol treatment for 24 h produced the strongest inhibitory effect (0.13±0.035, P<0.05). AQP-3 protein expression in cells treated with 25, 50, and 100 μmol/L propofol for 24 h (0.91±0.009, 0.60±0.020, and 0.57±0.006, respectively) and MMP-9 protein expression in cells treated with 50 and 100 μmol/L propofol for 24 h (0.65 ± 0.006 and 0.46 ± 0.021, respectively) were significantly lower than those in the control cells (P<0.05). Treatment with 25, 50, and 100 μmol/L propofol for 24 significantly lowered the number of invading cells (122.55 ± 17.20, 96.33 ± 5.82, and 74.33 ± 2.85, respectively) compared with the control group (199.33±23.88, P<0.05). Conclusion Treatment with 50 and 100 μmol/L propofol inhibits cell invasion by down-regulating the expression of AQP-3 and MMP-9 in A549 cells.