Armadillo (ARM)-repeat protein is involved in many biological processes, including cell–cell adhesion and the Wnt signaling pathway. However, the function of ARM-repeat protein in Bombyx mori has not been completely clarified. In this study, a gene encoding ARM-repeat protein was identified, which has an open reading fragment of 1923 bp, encoding a predicted 641 amino acid residues with a molecular weight of approximately 71.2 kDa. BmARM-like mRNA showed highest expression in hemolymph, significantly high expression levels in 4th instar, moth, and egg, stable high expression levels in the early embryonic development, relatively high expression levels in the 1st day and 5th day of the pupa stage, and highest expression levels in the molting stage. What’s more, BmARM-like protein could be detected by immunofluorescence in all analyzed tissues, including head, midgut, hemolymph, fat body, testis and ovary. More importantly, the relatively high expression level of BmARM-like mRNA were observed in BC9 (near-isogenic line) following BmNPV infection as compared to P50 (susceptible strain), which was further validated in the midgut of A35 (resistant strain). The expression levels of BmARM-like protein showed similar trends with transcriptional levels in the midgut following BmNPV infection. Based on the analysis above, we speculated that BmARM-like is involved in response against BmNPV infection.