Liver injury represents a continuum of pathophysiological processes involving a complex interplay between hepatocytes, macrophages, and hepatic stellate cells. The mechanism whereby these intercellular interactions contribute to liver injury and fibrosis is not completely understood. We report here that angiogenic factor with G patch and FHA domains 1(Aggfl) was downregulated in the livers of cirrhotic patients compared to healthy controls and in primary hepatocytes in response to carbon tetrachloride(CC14) stimulation. Overexpression of Aggfl attenuated macrophage chemotaxis. Aggfl interacted with NF-κB to block its binding to the Ccl2 gene promoter and repressed Ccl2 transcription in hepatocytes. Macrophages cultured in the conditioned media collected from Aggfloverexpressing hepatocytes antagonized HSC activation. Taken together, our data illustrate a novel role for Aggfl in regulating hepatic inflammation and provide insights on the development of interventional strategies against cirrhosis. Liver injury represents a continuum of pathophysiological processes involving a complex interplay between hepatocytes, macrophages, and hepatic stellate cells. The mechanism whereby these intercellular interactions contribute to liver injury and fibrosis is not completely understood. We report here that angiogenic factor with G patch and FHA domains 1 (Aggfl) was downregulated in the livers of cirrhotic patients compared to healthy controls and in primary hepatocytes in response to carbon tetrachloride (CC14) stimulation. Overexpression of Aggfl attenuated macrophage chemotaxis. Aggfl interacted with NF-κB to block its binding to the Ccl2 gene promoter and repressed Ccl2 transcription in hepatocytes. Macrophages cultured in the conditioned media collected from Aggregation of hepatocytes antagonized HSC activation. Taken together, our data illustrate a novel role for Aggfl in regulating hepatic inflammation and provide insights on the development of interventional strategies against cirrhosis.