Autophagy is an evolutionarily conserved lysosome-dependent degradative process that intracellular material is degraded to fuel starving cells and eliminate intracellular pathogens.The accumulation of autophagosomes could be due to both induction of autophagy and inhibition of autophagosome turnover.We first investigate that niclosamide acts not only as an autophagy inducer detected by autophagic flux and Atg16 staining followed by inhibition of mammalian target of rapamycin complex 1 (mTORC1), but also as a lysosome inhibitor to block the lysosome function measured by long-lived protein degradation which might due to lysosomal membrane permeabilization.According to niclosamide function, other common used small molecules that inhibit lysosome function show obvious inhibition on mTORC1 which can be rescued by enhanced Rag-mTORC1 interaction.Thus, we propose a new lysosome-mediated autophagic signaling model.Besides conventional blockage on lysosome degradation lysosome inhibitors also suppress mTORC1 activity by sensing lower concentration of amino acids inside lysosome which will further promotes autophagosome initiation.Therefore, the chemicals that inhibit lysosomal function should be considered carefully when we define their physiological role in autophagic process.