Schistosomiasis is one of the major human parasitic diseases in many developing countries that causing chronic ill health in humans. The present work aimed to study the possible curative role of Costus (Saussurea lappa) root extract against Schistosoma mansoni infection induced liver toxicity, cytokines, oxidative stress and DNA damage in mice. 40 adult male micewere divided into four groups (G1, control; G2, Costus; G3, infection with S. mansoni live cercariae; G4, S. mansoni infection followed by Costus treatment). By comparison to control, mice with S. mansoni infection exhibited significantly (p<0.01) higher levels of plasma TNF-α, faecal and hepatic eggs load, hepatic DNA damage and MDA, as well as significantly (p<0.01) lower levels of hepatic GSH, catalase and SOD. Meanwhile, by comparison to mice with S. mansoni infection, infected mice treated with Costus root extract had significantly (p<0.01) lower levels of faecal and hepatic eggs load, granuloma diameter, TNF-α in plasma, hepatic MDA, DNA damage, as well as significantly higher levels of hepatic GSH, catalase and SOD. The conclusion derived was that free radicals are formed by the host-parasite interaction because the parasite induces alterations in the hepatic antioxidants of the host to be able to scavenge the radicals as oxidative stress makes it difficult for the parasite to overpower the host's immune response.