Prostaglandin E2(PGE2) is an autocrine and paracrine signal in insects and other animals. Its signal pathways in target cells are well understood in mammalian system but not in insects. Here, we assessed PGE2 signaling in hemocytes of Spodoptera exigua through knocking-down of signal component genes by RNA interference (RNAi) and knocking-out (KO) of PGE2 receptor using CRISPR-Cas9. From S. exigua transcriptome, we selected hemocyte signaling components and analyzed their functions in cellular immune responses through RNAi. KO mutant against PGE2 receptor exhibited severely hampered larval development and adult fecundity.