SI113, a novel, potent and specific inhibitor of the Sgk1 kinase, is also able to strongly and consistently block, in vitro and in vivo, growth and survival of human hepatocellular-carcinomas, either used as a single agent or in combination with ionizing radiations. In the present paper we aim to study the effect of SI113 on human GBM cell lines with variable p53 expression. SI113 strongly affected the PI3K/mTOR pathway, evoking a pro-survival autophagic response in neurospheres.