CD133, a pentaspan membrane glycoprotein, is extensively used as a surface marker to identify and isolate stem-like cells. However, the molecular and biological functions of CD133 are not well understood. Here, we demonstrate that the Drosophila Prominin-like, a homology of mammalian CD133, regulates body size. We find that Prominin-like expression levels are regulated by ecdysone signaling and increase dramatically in the fat body during metarmorphsis. Interestingly, the prominin-like mutants exhibit bigger body size and excess body weight accompanied with higher fat deposits. Varied dilps transcriptional levels and up-regulated TOR are observed in the mutants. Whilst, overexpressing Prominin-like in insulin-producing cells (IPCs) induces a smaller body size. Taken together, these findings reveal that Prominin-like controls fly body size through affecting dilps and inhibiting TOR pathway, which may suggesting a novel function of CD133 on metabolism in cancer stem cells (CSCs) and cancers.