Chronic hepatitis B virus infection is a source of substantial global health problems, particularly in economically underdeveloped and/or developing countries. It is the primary cause of severe liver disorders such as liver fibrosis, cirrhosis, and hepatocellular carcinoma. The liver is connected by the bile duct to the small intestine that carries bile produced in the liver to the intestine. The liver is the initial organ exposed to materials originating from the gut including dietary compounds, bacteria, and their products. Human intestines harbor a wide diversity of the community of microbes which are collectively termed as gut microbiota. In chronic infection with the hepatitis B virus, microbial alteration of the gut is a source of systemic immune activation. Besides, gut permeability is altered in hepatitis B virus-infected patients with an increased bacterial translocation and endotoxin load in the portal vein that caused toll-like receptor activation in the liver, which facilitates immune-mediated liver injury. Toll-like receptors further triggered the host-wide inflammatory response by inducing signaling cascades such as nuclear factor-kappa B-linked pathways and by accelerating cytokine secretion like tumor necrosis factor-alpha, which evokes chronic inflammation and leads to liver lesion formation, fibrosis progression, and cirrhosis and hepatocellular carcinoma development. In conclusion, changes in intestinal flora play an important role in encouraging the production of chronic infection with the hepatitis B virus. Therefore, careful attention should be given to the maintenance of intestinal microecology of patients which can provide a sound foundation for the treatment of chronic infection with the hepatitis B virus.