BMI1 belongs to the polycomb-repressive complex 1 (PRC1) family of genes that are conserved chromatin silencers. These are essential for maintaining both the normal and cancerous stem cell state. In this study, we evaluated the effect of siRNA-mediated BMI1 knockdown on tumor cell properties such as invasion, migration, and apoptosis, as well as on cell signaling pathways responsible for tumor progression in the human glioma cell line, U251. Knockdown of BMI1 induced apoptosis by activating cleavage of PARP and caspase-3. It also decreased the expression of anti-apoptotic proteins, survivin, XIAP, Bcl-xL, and Mcl1. Additionally, BMI1 knockdown significantly decreased cell invasion and cell migration ability. BMI1 knockdown also decreased the phosphorylation of Akt/FOXO1/3a signaling proteins. Our results suggest that BMI1 knockdown induces apoptosis and decreases cell invasion and cell migration. Moreover, we believe these phenomenona are associated with decreased phoshorylation of Akt signaling proteins, which contributes to cancer progression.