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Integrin inhibitors may change conformational and dynamical properties of integrin, but its molecular properties in this process is not clearly understood. Tumstatin is an anti-angiogenesis protein derived from collagen XVIII, but little is known about how tumstatin applies its antiangiogenic and antitumor effects. It has been reported that 18 amino acids fragment of tumstatin has anti-tumor activities similar to tumstatin. We used molecular docking and molecular dynamic simulations to describe inhibitor activity of peptide in molecular level. We described the binding of this peptide to Hybrid/EGF-4 interface and that these interactions might contribute to improved hydrophobic interactions at these regions and also fixed the mobile domains of integrin. In the complex, we recognized a novel binding site on integrin for integrin inhibitors that may have critical role in integrin inhibition. These results support the idea that hydrophobic interactions between Hybrid/EGF-4 domain and peptide-anti tumor might contribute to stability of bended state and therefore inhibit integrin activation.  Our finding can be applied to understand the mechanism of out-in pathway integrin signaling and development of integrin targeted drug.