Abstract: As an asexual reproduction mode of moon jellyfish Aurelia coerulea podocysts play an important role in resist hostiling environment, maintaining and expanding the population of polyps. However, relevant genes that drive podocysts forming are still unclear. This study developed the transcriptome profile and performed bioinformatics analyses between podocysts forming and non-forming polyps for the first time, and explored molecular mechanism of podocysts formation. A total of 44 873 genes were detected by transcriptome sequencing, while 200 differential genes were harvested after filtration, of which 95 genes were significantly up-regulated and 105 genes were significantly down-regulated in podocysts forming polyps. Further analysis discovered vitellin genes (VTG-1 and VTG-2) and hornerin genes (Hornerin) may regulate the nutrients reserve and chitin formation of podocysts. In addition, GO and KEGG analysis showed that biological processes involved in cell division and differentiation such as ErbB pathway and Hedgehog pathway were significantly down-regulated in podocysts forming polyps, while process that involved in cell migration such as basement membrane organization, positive regulation of locomotion were significantly enriched, indicating the processes played an important role in podocysts formation. Thus, this study provides a theoretical basis for the research of adaptive mechanisms when Aurelia coerulea polyps facing with hostile environment.