Drosophila metamorphosis is associated with substantial metabolic activity involving cell death and cell proliferation leading to differentiation of adult tissues and structures. Unlike other larval tissues, Malpighian tubules (MTs) exhibit apoptotic immunity and do not undergo cell death but are carried over to the adult with some cell reorganisation. They persist despite the fact that they express apoptotic proteins and caspases. In the present study, we analysed the global transcription changes in MTs and compared with salivary glands, to decipher the biology of MTs. Gene set enrichment analysis indicated reduced expression of many ecdysone induced genes, including the critical regulator of cell death, E93 in MTs. We hypothesize that reduction of E93 could be because of over expression of ecdysone oxidase, which is high in MTs and is responsible for regulation of hormone titer by degradation of ecdysone. Ectopic expression of E93 in MTs results in cell death through autophagy. Fork head, which is crucial for survival, is enriched in the MT transcriptome, and its down regulation in MTs could be consequent to over expression of E93. Together our data suggests that the cascade of events initiated by ecdysone mediates survival of MTs through concerted action of multiple factors.