Objective: To test whether IL-1 RI/My088-TIR mimic AS-1 can work as a new compound that targeted at blocking MyD88-dependent signaling pathway, we investigated the physical structure and biological function of AS-1. Methods:The crystallographic structure of AS-1 was examined by 1H nuclear magnetic resonance. The toxicity of AS-1 was measured with Methyl thiazolyl tetrazolium(MTT) assay. The effect of AS-1 on phosphorylation state of p38 MAPK and IRAK-1 was observed with Western blot. Results:The crystallographic details of AS-1 demonstrated that it was a tri-peptide sequence[(F/Y)-(V/L/I)-(P/G)] of the IL-1RⅠ-TIR domain BB-loop. No toxicity of AS-1 was shown to HEK 293A cells. The phosphorylation of p38 MAPK, induced by IL-1β significantly increased from those in the control group. AS-1 significantly reduced the phosphorylation of p38 MAPK induced by IL-1β. IL-1β increased the phosphorylation of IRAK-1 significantly, which was prevented by AS-1. Conclusion:AS-1 is a competitive mimic between IL-1RⅠ-TIR and MyD88-TIR domain, which most likely interferes with MyD88-dependent signaling pathway.