The aim of this work was to explore the effect of dehydroepiandrosterone (DHEA) on the establishment, growth and reproduction of the metacestode stage of the tapeworm Taenia crassiceps, both in vivo and in vitro. Administration of DHEA prior to infection in mice of both sexes reduced the parasite load by 50% compared with untreated mice. This protective effect was not associated with the immune response, since there was no effect of DHEA treatment on mRNA levels of IL-2, IFN-gamma, IL-4 or IL-10. DHEA treatment of infected mice increased androgen receptor expression in splenocytes of both sexes. Moreover, in vitro treatment of T. crassiceps with DHEA reduced reproduction, motility and viability in a dose- and time-dependent fashion. Results indicate that DHEA has strong negative direct modulatory effects on murine cysticercosis. We suggest the use of hormonal-analogues for protective purposes as a therapeutic approach to prevent murine cysticercosis.