GRIM-19 (genes associated with retinoid-IFN-induced mortality-19) is a subunit of mitochondrial respiratory complex I in mammalian systems. However, its function in vivo is not really understood. We cloned GRIM-19 and explored its function and hormonal regulation in insect, the cotton bollworm, Helicoverpa armigera. The results showed that Ha-GRIM-19 was highly expressed during the larval stage. Its transcript levels could be upregulated by juvenile hormone (JH) analog methoprene or by methoprene plus 20E. The methoprene-upregulated transcription enhancement of Ha-GRIM-19 was mediated by the transcription factor Ha-Met1, the putative receptor of JH. Other transcription factors Ha-USP1 and Ha-Br-Z2 suppressed the action of methoprene in inducing Ha-GRIM-19 expression, but Ha-Br-Z2 introduced interaction between 20E and methoprene in upregulation of Ha-GRIM-19. The knockdown of Ha-GRIM-19 by RNA interference in larvae and in insect cell line induced programmed cell death. These data imply that Ha-GRIM-19 plays role in keeping the normal cellular growth and it is able to be upregulated by methoprene through putative JH receptor Met.