Vitamin D deficiency is coprevalent with various liver diseases, indicating the role of vitamin D in maintaining liver homeostasis. In this study, we observed that the hepatic 25-hydroxylation of VD is critical for intestinal innate immunity through VD signaling in the small intestine for maintaining Paneth cell functions. Conversely, failure of biogenesis of VD in the liver impairs intestinal immunity, leading to gut dysbiosis and endotoxemia, which promotes liver fibrogenesis.