The Baculoviridae is a large family of pathogens that are infectious for arthropods, particularly insects of the Lepidoptera. Nucleopolyhedroviruses (NPVs), a genus of Baculoviridae, have a large circular, supercoiled, and double-stranded DNA genome packaged into rod-shaped virions. The Bombyx mori NPV (BmNPV), an NPV pathogenic for B. mori, is known to potentially encode 136 proteins. Using the B. mori genome information, we found that 15 of 136 BmNPV proteins (11%) show significant similarity to the B. mori proteins. Among them, genes encoding nine proteins can be deleted in B. mori cultured cell line BmN by homologous recombination, indicating that these genes are dispensable for normal virus production. Interestingly, most of non-essential auxiliary genes encode proteins controlling host physiology at cellular and/or organismal levels: ecdysteroid UDP-glucosyltransferase inactivates an insect molting hormone ecdysone, protein tyrosine phosphatase is involved in wandering behavior at the late stage of infection, fibroblast growth factor induces host cell chemotaxis, and chitinase and cathepsin are required for postmortem host liquefaction. Deletion analysis of other non-essential genes also showed that three of them are viral pathogenicity factors for B. mori. These findings suggest that the modern lepidopteran baculovirus may have acquired auxiliary genes from an ancestral host insect to control host physiology and to increase the efficiency of virus transmission in nature.