The immunological mechanisms by which hepatitis B virus (HBV) initiates and maintains acute or chronic infection, even the formation of cirrhosis and hepatocellular carcinoma, are still undefined. An increasing number of studies have shown that intestinal flora regulate immune homeostasis, and, thus, protect the immunologic function against hepatitis virus infection. In this article, we discuss gut microbiota and its potential immune effects against HBV infection. It may provide a novel insight into the pathogenesis of HBV infection, as well as a potential therapeutic target to HBV-related disease.