In the present study, we investigated the involvement of the P2Y<sub>11</sub> receptor using its specific antagonist NF157 in some key aspects of HBx-induced liver disease in human MIHA hepatocytes, including mitochondrial dysfunction due to compromised mitochondrial membrane potential (MMP), oxidative stress resulting from overproduction of reactive oxygen species (ROS) and decreased antioxidant glutathione (GSH), production of proinflammatory cytokines and chemokines such as interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and chemokine (C-X-C motif) ligand 2 (CXCL2), as well as activation of cellular signaling pathways including the p38/mitogen-activated protein kinase (p38/MAPK) and nuclear factor-κB (NF-κB) pathways.