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Cadherin, aminopeptidase N (APN) and alkaline phosphatase (ALP) have been characterized as Cry receptors. In this study, comparative genomic analysis of the 3 receptor families was performed in 7 insects. ALPs and APNs are divided into three and eight clades in phylogenetic trees, respectively. ALPs in clade 3 and APNs in clade 1 contain multiple paralogs within each species and most paralogs are located closely in chromosomes. Drosophila melanogaster has expanded APNs in clade 5 and were lowly expressed in midgut. Cadherins are divided into 16 clades; they may diverge before holometabolous insect speciation except for BtR and Cad89D‐like clades. Eight insects from different orders containing BtR orthologs are sensitive to Cry1A or Cry3A, while five species without BtR are insensitive to both toxins. Most APNs in clade 1, several ALPs in clade 3, BtR and Cad89D‐like genes were highly or moderately expressed in larval midgut of Spodoptera litura and the other six species, and several members in these clades have been identified as Cry receptors. Expressions of putative S. litura Cry receptors in the midgut after exposing to Bt toxins were also analyzed. [ABSTRACT FROM AUTHOR]