Current advances in reverse vaccinology based on the principle of "sequence-structure-function" and such integrated platform technologies as immunoinformatics, computer-aid design, and various high-throughput omics (including genomics, transcriptomics and proteomics) may pave a new way for the discovery of candidate vaccine molecules against schistosomiasis. Both theoretical prediction and experimental approaches conventionally used in the field of reverse vaccinology are briefly introduced in this review; and the applications of these approaches to screening and confirming candidate Schistosoma vaccine molecules are also summarized. Furthermore, potential research prospects of the application of reverse vaccinology to Schistosoma vaccine development are discussed by simulating immune effect mechanisms of immunization with radiation-attenuated cercaria vaccine in animal hosts and naturally acquired immunity in human population.