RNA interference; Schistosoma mansoni; Smtal-9; immunization; protection. The tegument of Schistosoma mansoni is involved in essential functions for parasite survival and is known to stimulate immune responses in pre-clinical vaccine trials. Smtal-9, a member of the tegument-allergen-like (TAL) family, is one of the components of the tegument of schistosomula recognized by sera from immunized and protected mice. In this work, we assessed the role of Smtal-9 in parasite survival using the RNAi approach. Also, we cloned and expressed a recombinant form of Smtal-9 and evaluated its ability to induce protection in mice. Smtal-9 knockdown did not impact parasite survival in vitro, but significantly decreased schistosomula size. Additionally, significant reduction in both parasite and egg burdens were observed in mice inoculated with Smtal-9-knockdown schistosomula. Immunization using the Smtal-9 as an antigen conferred partial protection against challenge infection. Overall, our results indicate that Smtal-9 is a candidate target for drug and/or vaccine development due to its important role in parasite biology and survival.