BACKGROUNDCockroaches are widely acknowledged as significant vectors of pathogenic microorganisms. The densovirus PfDNV infects the smoky‐brown cockroach Periplaneta fuliginosa and causes host mortality, which identifies the PfDNV as a species‐specific and environmentally friendly biopesticide. However, although the biochemical characterization of PfDNV has been extensively studied, the immune response against PfDNV remains largely unclear.RESULTSHere, we investigated the replication of PfDNV and its associated pathological phenotype in the foregut and hindgut. Consequently, we dissected and performed transcriptome sequencing on the foregut, midgut, and hindgut separately. We revealed the up‐regulation of immune response signaling pathway JNK and apoptosis in response to viral infection. Furthermore, knockdown of the JNK upstream gene Ben resulted in a decrease in virus titer and delayed host mortality.CONCLUSIONTaken together, our findings provide evidence that the Ben‐JNK signaling plays a crucial role in PfDNV infection, leading to excessive apoptosis in intestinal tissues and ultimately resulting in the death of the host. Our results indicated that the host response to PfDNV fosters viral infection, thereby increasing host lethality. This underscores the potential of PfDNV as a viable, environmentally friendly biopesticide.This article is protected by copyright. All rights reserved.