Hepatolithiasis is one of the common hepatobiliary diseases. It has been confirmed that biliary infection, cholestasis and epithelial mesenchymal transformation are important factors for the occurrence and the development of this condition, and recent studies found that inflammation mediated by LPS/TLR4 pathway plays a crucial role in the pathogenic processes of these factors. Here, the authors address the potential actions and relevant mechanisms of LPS/TLR4 signaling pathway in hepatolithasis, so as to provide new paths to the mechanism research as well as prevention and treatment of hepatolithiasis.