Using dual-luciferase reporter assays and transfection of miR-383-5p mimics and inhibitors into LX-2 cells, we confirmed that miR-383-5p directly targeted the 3′ untranslated region (UTR) of PRDX3, leading to decreased mRNA levels of PRDX3. AAV8-mediated miR-383-5p overexpression and PRDX3 knockout in the mice infected with S. japonicum led to increased hepatic ROS and promoted the schistosomiasis-induced liver fibrosis. This evidence concerns the gene PRDX3 and Hepatic fibrosis.