Human self-domestication (i.e., the presence of traits in our species that are commonly found in domesticated animals) has been hypothesized to have contributed to the emergence of many human-specific features, including aspects of our cognition and behavior. Signs of self-domestication have been claimed to be attenuated in individuals with autism spectrum disorders (ASD), this conceivably accounting for facets of their distinctive cognitive and behavioral profile, although this possibility needs to be properly tested. In this study, we have found that candidate genes for mammal domestication, but not for neural crest development and function, are significantly dysregulated in the blood of subjects with ASD. The set of differentially expressed genes (DEGs) is enriched in biological and molecular processes, as well as in pathological phenotypes, of relevance for the etiology of ASD, like lipid metabolism, cell apoptosis, the activity of the insulin-like growth factor, gene expression regulation, skin/hair anomalies, musculoskeletal abnormalities, and hearing impairment. Moreover, among the DEGs, there are known candidates for ASD and/or genes involved in biological processes known to be affected in ASD. Our findings give support to the view that one important aspect of the etiopathogenesis of ASD is the abnormal manifestation of features of human self-domestication.