Autophagy is an evolutionarily conserved protein degradation pathway in eukaryotes that plays key role in a number of pathological conditions including cancer. Understanding the mechanism of autophagy will offer hope for the development of new therapeutic approaches for cancer treatment. To elucidate the role of autophagy in tumorigenesis or tumor progression, we explored the expression of autophagy-associated proteins in tumor tissues. Our results showed that low expression of Beclin 1 was significantly associated with poor prognosis in ovarian tumors, colon cancers with stage IIIB, lymphoma. We also found that the patients with lower level of ULK1 had a significant shorter cancer-related survival time and distant metastasis-free survival time. To understand whether anticancer drugs induces autophagy in cancer cells, topotecan and ceramide were employed. The results showed that activation of JNK pathway can phosphorylate c-Jun and promote c-Jun binding to the promoters of Beclin 1, LC3 and Sestrin 2 to upregulate Beclin 1, LC3 and Sestrin 2 expression, which plays a key role in anticancer agentsinduced autophagy in cancer cells. We also found that Beclinacetylated by p300 at lysine residues 430 and 437. The phosphorylation of Beclin 1 at S409 by CK1 is required for the subsequent p300 binding and Beclin. Beclin 1 acetylation inhibits autophagosome maturation and endocytic trafficking by promoting the recruitment of Rubicon. In tumor xenografts, the expression of 2KR mutant Beclin 1 leads to enhanced autophagosome maturation and tumor growth suppression. In order to explore the role of autophagy in cancer treatment, our investigation showed that Rhabdastrellic acid-A, an isomalabaricane triterpenoid isolated from the sponge Rhabdastrella globostellata, induced autophagy of cancer cells. SYUIQ-5, previously identified by us as a novel G-quadruplex stabilizer and potent telomerase inhibitor, inhibited proliferation of cancer cells, triggered a rapid and potent telomere DNA damage response and obviously induced autophagy. These phenomena may primarily depend on the delocalization of TRF2 from telomere. We found that wild-type p53 can activate AMPK, inhibit mTORC1 and promote colon cancer cells survival by enabling cytoprotective autophagy in response to topotecan treatment. In contrast, the inhibition of autophagy alleviated the anti-tumour effect of topotecan treatment in p53 mutant or knockout colon cancer cells both in vitro and in vivo. We also found that topotecan, a topoisomerase I inhibitor, and cisplatin induced DNA damage and activated ATM, which phosphorylates PTEN at serine 113 and further regulates PTEN nuclear translocation in A549 and HeLa cells. After nuclear translocation, PTEN induces autophagy, in association with the activation of the p-JUNSESN2/AMPK pathway, in response to topotecan. Our researches show that decreased autophagy-related protein expression is associated with tumor progression and poor prognosis in ovarian cancer, breast cancer, colon cancer. We also found that some anticancer agents-mediated autophagyassociated cell death or survival dependent of cancer cell context. Therefore, understanding the mechanisms of autophagy and the role of autophagy in cancers will facilitate novel therapeutics for cancer.