Tumor necrosis factor-induced protein 8(TNFAIP8), the first identified member of the TNFAIP8 family, shares considerable sequence homology with members of this family. It is expressed in a wide variety of human normal tissues, with relatively higher levels in lymphoid tissues and placenta. The present study was designed to examine the effect of TNFAIP8 on T-cell-mediated immunity secondary to burn injury. Sixty male mice were randomly divided into four groups as follows: sham burn group, burn group, burn with TNFAIP8-siRNA transfection group, and burn with negative control transfection group, and they were sacrificed at designated time points. CD4+ T cells were isolated using MACS microbeads. T-Cell proliferation was analyzed with MTT assay, and IL-2, soluble IL-2R, IL-4, interferon-γ (IFN-γ) were determined with enzyme-linked immunosorbent assay kits. It was found that CD4+ T lymphocyte proliferative activity was significantly down-regulated when TNFAIP8 gene was silenced by siRNA in mice at 24 h post burn. Down-regulation of TNFAIP8 can significantly decrease expression levels of IL-2 and soluble IL-2R at 24 h after thermal injury. These results demonstrated that TNFAIP8 appeared to be involved in the immune regulation of CD4+ T lymphocytes, and the decreased expression of TNFAIP8 could affect T lymphocyte functions after thermal injury.