Schistosoma japonicum causes schistosomiasis in humans and livestock in the Asia-Pacific region. We assembled more than 43,700 S. japonicum expressed sequence tags and conducted comparative genomic analyses between S. japonicum and its human host. Some schistosome genes showed exceptionally high similarity in nucleotide sequence to their human homologues, of which five exhibited anomalous phylogeny and human codon usage bias. The most plausible explanation for their presence is horizontal gene transfer from host to parasite. Functional evidence suggests that S. japonicum might exploit host endocrine and immune signals for cell development and maturation via these host-like genes.