Abstract Cadherins have been described as one the main functional receptors for the toxins of the entomopathogenic bacterium, Bacillus thuringiensis ( Bt ). With the availability of the whole genome of Plutella xylostella , different types of cadherins have been annotated. In this study we focused on determining those members of the cadherin‐related proteins that potentially play a role in the mode of action of Bt toxins. For this, we mined the genome of P. xylostella to identify these putative cadherins. The genome screening revealed 52 genes that were annotated as cadherin or cadherin‐like genes. Further analysis revealed that six of these putative cadherins had three motifs common to all Bt ‐related cadherins: a signal peptide, cadherin repeats and a transmembrane domain. From the six selected cadherins, only P. xylostella cadherin 1 ( PxCad1 ) was expressed in the larval midgut and only the silencing of this gene by RNA interference (double‐stranded RNA feeding) reduce toxicity and binding to the midgut of the Cry1Ac type toxin from Bt. These results indicate that from the whole set of cadherin‐related genes identified in P. xylostella , only PxCad1 is associated with the Cry1Ac mode of action.