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Plant secondary metabolites (PSM) influence the susceptibility of insect herbivores to entomoviruses, but the apoptosis mechanism is not clear. Among plant hosts screened, the level of coumarin is correlated with NPV-mediated mortality, with high coumarin levels associated with high mortality and low coumarin levels with low mortality. Flow cytometry and morphological experiments showed that coumarins increased the apoptosis rate in NPV-infected larvae. miRNA transcriptomic analysis of coumarin-exposed larvae identified downregulation of miR-8 and miR-6497-3p, which negatively correlate with expression of pro-apoptotic kinases MAPK and ASK1. In addition, miR-9c-5p is upregulated, suppressing the apoptosis inhibitor 14-3-3 protein zeta. Our study suggests plant coumarins increase the susceptibility of larvae to NPV through miRNA-mediated regulation of apoptotic pathways. These findings suggest viral biocontrol efforts may be more successful on certain host plants, and provide molecular insight into how plant defense chemicals synergize with entomoviruses to control agricultural pests.