In the present study, we demonstrate for the first time that either individual or simultaneous downregulation of uPAR and cathepsin B using siRNA decreased Bcl-2 expression and increased Bax expression in U251 glioma cells and 5310 glioma xenograft cells (in vitro), and in brain tumor tissue sections and tissue lysates (in vivo). The gene discussed is CTSB; the disease is central nervous system cancer.