Schistosomes undergo complicated migration in final hosts during infection, associated with differential immune responses. It has been shown that CD4 T cells play critical roles in response to infections and accumulated documents have indicated that miRNAs tightly regulate T cell activity. However, miRNA profiles in host T cells associated with infection remain poorly characterized. Therefore, we undertook the study and systematically characterized T cell miRNA profiles from the livers and blood of infected C57BL/6J mice at 14- and 21-days post-infection. We observed 508 and 504 miRNAs, in which 264 miRNAs were co-detected in T cells isolated from blood and livers, respectively. The comparative analysis of T cell miRNAs from uninfected and infected C57BL/6J mice blood showed that expression was significantly downregulated and linked to various T cell immune responses and was highly upregulated, associated with Wnt signaling and pluripotency, Delta notch signaling pathways, Whereas hepatic T cells showed , , , and were differentially expressed compared to the uninfected control. The different expressions of some miRNAs were further corroborated in isolated T cells from mice and cultured EL-4 cells treated with worm antigens by RT-qPCR and similar results were found. In addition, bioinformatics analysis combined with RT-qPCR validation of selected targets associated with the immune system and parasite-caused infectious disease showed a significant increase in the expression of , , , and and a decreased expression of , , , , , , , , , , and . Overall, these results unveil the comprehensive repertoire of T cell miRNAs during infection, suggesting that the circulatory (blood) and liver systems have distinct miRNAs landscapes that may be important for regulating T cell immune response. Altogether, our findings indicated a dynamic expression pattern of T cell miRNAs during the hepatic stages of infection.