Our results demonstrate that PKM2 physically interacts with and increases the stability of IGF-1R protein by mediating binding between HSP90 and IGF-1R, whereas PKM2 knockdown decreases the basal level of IGF-1R expression and inhibits AKT activation, the key downstream effector of IGF-1R signaling, consequently increasing apoptotic cancer cell death during hypoxia. Here, AKT1 is linked to cancer.