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<i>Mucor hiemalis</i> BO-1 is an entomopathogenic fungus that infects <i>Bradysia odoriphaga</i>, a destructive root maggot. <i>M. hiemalis</i> BO-1 possesses stronger pathogenicity to the larvae than to other stages of <i>B. odoriphaga</i>, and provides satisfactory field control. However, the physiological response of <i>B. odoriphaga</i> larvae to infection and the infection mechanism of <i>M. hiemalis</i> are unknown. We detected some physiological indicators of diseased <i>B. odoriphaga</i> larvae infected by <i>M. hiemalis</i> BO-1. These included changes in consumption, nutrient contents, and digestive and antioxidant enzymes. We performed transcriptome analysis of diseased <i>B. odoriphaga</i> larvae, and found that <i>M. hiemalis</i> BO-1 showed acute toxicity to <i>B. odoriphaga</i> larvae and was as toxic as some chemical pesticides. The food consumption of diseased <i>B. odoriphaga</i> after inoculation with <i>M. hiemalis</i> spores decreased significantly, and there was a significant decrease in total protein, lipid, and carbohydrates in diseased larvae. Key digestive enzymes (protease, α-amylase, lipase, and cellulase) were significantly inhibited during infection. Peroxidase maintained high activity, and the activity of other antioxidant enzymes (catalase, superoxide dismutase, and glutathione S-transferases) first increased and then decreased. Combined with the transcriptional signatures of diseased <i>B. odoriphaga</i> larvae, <i>M. hiemalis</i> BO-1 infection resulted in decreased food consumption, reduced digestive enzyme activity, and altered energy metabolism and material accumulation. Infection was also accompanied by fluctuations in immune function, such as cytochrome P450 and the Toll pathway. Therefore, our results laid a basis for the further study of the interactions between <i>M. hiemalis</i> BO-1 and <i>B. odoriphaga</i> and promoted the genetic improvement of entomopathogenic fungi.