Objective：This study aims to evaluate the effect of Nerve injury-induced protein 1（Ninj1）in myeloid-derived macrophages on liver ischemia/reperfusion（IR）-induced immune inflammatory response. Methods：Peripheral blood mononuclear cells（PBMC） were collected from 6 patients who undergone hepatic portal occlusion（hepatic portal occlusion group）during hepatectomy and another 6 patients who had no hepatic portal occlusion（control group）. RT-PCR and Western blot were performed to compare the expression of Ninj1 in PBMC of pre-operation and post-operation between the two groups. Murine bone marrow derived macrophages（BMDM）treated with lipopolysaccharide（LPS）were used to evaluate the role of Ninj1 in regulating macrophage inflammatory response in vitro. A murine liver partial warm ischemia reperfusion model was established to determine the role of Ninj1 in liver IR injury and hepatic inflammation. Results：In the hepatic portal occlusion group，the mRNA and protein levels of Ninj1 in PBMCs of post-operation were significantly higher than that in PBMC of pre-operation（P < 0.05），while no obvious change was observed in the control group. Compared with the PBS group，Ninj1 was significantly upregulated in murine BMDM in response to LPS stimulation. Knockdown of Ninj1 in BMDM by siRNA in vitro markedly reduced LPS-induced inflammatory cytokine secretion（P < 0.05）. Specific blockade of Ninj1 in macrophages obviously attenuated liver IR injury and hepatic inflammation in vivo（P < 0.05）. Conclusion：Liver IR significantly activated Ninj1 in patients’ PBMCs. Inhibition of Ninj1 can mitigate macrophage inflammatory response leading to attenuation of liver IR injury in mice.