Objective To explore the effect of small interfering RNA (siRNA)-mediated cathepsin D (CD) knock-down on biological behavior of U87 cells. Methods CD-siRNA,scramble siRNA and control siRNA mediated by lipofectamin were introduced into the U87 cells,respectively.The silencing effect of CD was verified by RT-PCR and Western blotting in terms of CD mRNA and protein expressions. The cell viability of scramble and CD siRNA treated U87 cells was measured by MTT on 1-5 d after transfection. The invasive potential of scramble and CD siRNA treated U87 cells was measured by Transwell coated with Matrigel 48 h after transfection. Results Forty-eight h after transfection, mRNA and protein expressions of CD in CD siRNA treated U87 cells were remarkably reduced as compared with those in the scramble siRNA and control siRNA treated U87 cells (P＜0.05).The absorbance (A value) of CD siRNA treated U87 cells was significantly lower than that in the scramble siRNA treated U87 cells 2,3,4 and 5 d after transfection (P＜0.05); and the invasive potential of CD siRNA treated U87 cells was suppressed significantly as compared with that in the scramble siRNA treated U87 cells (P＜0.05). Conclusion CD has the potential to be a promising therapeutic target.