It was predicted that TLR8 had potential relationship with the expressions of cytokines IFN-α and IL-1β through mediating expressions of TRAF6. C. perfringens infection suppressed the expression of TLR8 in inoculated piglets, which was relatively higher expressed in IR group than that in IS group, interestingly, IFN-α was correspondingly higher expressed in IR group than in IS group, as well as expression of IL-1β at 1–3 dpi. Here, TLR8 is linked to infection due to clostridium perfringens.