Neuroblastoma (NB) is common in the pediatric tumors with low cure rate and high mortality, drug resistance makes chemotherapy more difficult, it threaten to children's health seriously. 1H-indole-2, 3-dione (isatin) is a second-hand of derivative of anticarcinogen indirubin which had been shown to be a monoamine oxidase inhibitor and have antitumor activity, in this study, we explained that SH-SY5Y cells was add to isatin at a dose-dependent level ranging from 50 to 200 µmol/L were capable of inhibiting tumor cell growth, included triggering apoptosis and inhibiting proliferation, invasion and metastasis, and assess ed the potential anticancer capability of isatin on the induction of autophagy. The experimental result showed that cell SH-SY5Y disposed with isatin could induce autophagy effectively, at the same time, it also help suppress the growth of tumor cells. Furthermore , the article indicated that the induction of autophagy of isatin-mediated occurred in inhibition- lysine-specific demethylase 1(LSD1) and sestrin2 (SESN2) - dependent manner. Furthermore, we identified that SH-SY5Y cells after treating with isatin induced SESN2 expression via a mTOR-dependent signal pathway, which mechanism is that isatin inhibit LSD1-enzyme activation and combine the promoter regions of SESN2, so that given rise to a significant transcriptional induction of SESN2. In addition , western blot analysis indicated that SH-SY5Y cells with isatin-exposed can regulated activity of LC-3, Beclin1 and p62 which are correlated with autophagy. Collectively, all the results from this study illistrated that adding to isatin could occur to induce autophagy and restrain NB cell SH-SY5Y growth through mTOR-dependent transcriptional induction of SESN2, this supplied a new mechanism for understanding the anti-tumor ability of isatin on NB. Taken together, this paper demonstrate that isatin is a promising candidate for treating NB.