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Schistosoma genus is one of trematode worms causing Schistosomiasis which is responsible for high rates of morbidity. Moreover, the disease induced hepatosplenomegaly, liver fibrosis and cirrhosis. The deposited and trapped eggs in hepatic peri-sinusoidal spaces induce granulomatous inflammation. The known anti-schistosomal drugs showed resistance so it was necessary to find a new anti-schistosomal treatment. Technologies such as nanoparticles are being used to improve or replace today’s therapies. Nanoparticles have advantages over today’s therapies because they can be engineered to have certain properties. Selenium nanoparticles have high bioavailability and antioxidant activities so it attracted wide spread attention. In the present study, selenium nanoparticles injection to schistosome-infected mice ameliorated the hepatic histopathology and decreased the granulomas diameters. Moreover, the treatment increased the glutathione level while; the levels of nitrite/nitrate and malondialdahyde were decreased significantly. Subsequently, the results indicate that the selenium nanoparticles may act as anti-schistosomal drug in infected mice with Schistosoma mansoni.