The effect of Laennec, a hydrolyte of human placenta, on immune-mediated liver injury was investigated in vivo and in vitro in murine. Vena caudalis administration of concanavalin A (Con A) was employed to establish an in vivo liver-injury model, and in vitro hepatotoxicity was induced by 8 h interaction between Con A pre-treated hepatocytes and Con A-stimulated autologous splenic lymphocytes. Laennec was used for pre-treatment in the two models. Laennec decreased biochemical marker activity (alanine aminotransferase, ALT; lactate dehydrogenase, LDH) in serum and recovered the activity of superoxide dismutase (SOD) and myeloperoxidase (MPO), as well as the content of malondialdehyde (MDA) and nitric oxide (NO) in liver tissue. We also found that the DNA ladder induced by Con A in vivo was attenuated by Laennec. Furthermore, the leakage of aspartate aminotransferase (AST) and LDH in the supernatant of the co-culture system was decreased by addition of Laennec. Potential protective mechanisms were elucidated by DNA fragmentation assay and intercellular adhesion molecule-1 (ICAM-1) induction/inhibition experiments. Results showed that ICAM-1, which is related to the interaction between hepatocytes and lymphocytes, was inhibited by Laennec. These findings indicated that Laennec has potent activity against immune-mediated liver injury.