The aim of the present study was to investigate the protective effect of SP600125, a selective c-Jun N-terminal kinase inhibitor, in brain death-induced liver injury. All 40 Sprague–Dawley rats are anesthetized. Analysis of liver histology, function, JNK phosphorylation status, as well as apoptosis related protein was evaluated in this study. As a result, SP600125 diminished the increased phosphorylation of JNK, whereas, expression of total JNK in the liver remained unchanged compared with the sham control and was not affected by SP600125. At the same time, SP600125 attenuated Bax translocation to mitochondria and the release of cytochrome c induced by brain death. Furthermore, the activation of caspase-3 and apoptosis induced by brain death was also significantly suppressed by the administration of SP600125. The results obtained from the present study suggested that targeting the JNK pathway provided a therapeutic target in liver injury induced by brain death.