Objective To explore the effect of lidocaine ( LID) on ischemia-reperfusion injury in orthotopic liver transplantation (OLT) rats and to analyze its mechanism of action. Methods Sixty rats were randomly divided into Verteporfin group, high-dose LID( High LID) , medium-dose LID( Medium LID) , low-dose LID( Low LID) , Model and Control groups,on average. The rest of the rats except the control rats were used to establish OLT models. Observe the pathological changes in liver tissue were with hematoxylin-eosin staining. Serum aspartate transaminase ( AST ) , total bilirubin ( TBIL) , lactate dehydrogenase ( LDH) activities and alanine transaminase (ALT) were detected. Measure liver tissue levels of proinflammatory factors tumor necrosis factor-α ( TNF-α) , interleukin ( IL) -6, IL-1β, and IL-10 with enzyme-linked immunosorbent assays. Reactive oxygen species ( ROS ) was detected by a fluorescence probe.Malondialdehyde (MDA) was detected by the thiobarbituric acid colorimetric method . Superoxide dismutase ( SOD) was detected by nitrogen blue tetrazole colorimetry. Glutathione peroxidase ( GSH-Px) was detected by a spectrophotometry method . Apoptosis of liver histiocytes was detected by in situ end labeling. Detect the expression of mammalian STE20 like protein kinase (MST1) , phosphorylation ( p) -MST1, large tumor suppressor factor 1 ( LATS1) , p-LATS1, Yes associated protein (YAP) , p-YAP, and apoptosis-related proteins B-cell lymphoma 2 ( Bcl-2) and Bcl-2 related X protein ( Bax) with Western blot. Results Compared with the Control group, liver tissue in Model group rats showed injury, liver cell necrosis, and a large degree of inflammatory cell infiltration. Moreover, the cell apoptosis rate; serum AST, ALT, TBIL,and LDH activities; and liver tissue levels of TNF-α, IL-6, IL-1β, MDA, ROS, and Bax were significantly increased.Furthermore, liver tissue levels of IL-10, SOD, GSH-Px, Bcl-2, p-MST1 / MST1, p-LATS1 / LATS1, and p-YAP / YAP proteins were significantly reduced ( P< 0. 05) . Compared with the Model group, liver tissue injury was reduced in Low LID, Medium LID, and High LID groups. The cell apoptosis rate; serum AST, ALT, TBIL, and LDH activities; and liver tissue levels of TNF-α, IL-6, IL-1β, MDA, ROS, and Bax were significantly reduced. Moreover, liver tissue levels of IL10, SOD, GSH-Px, Bcl-2, p-MST1 / MST1, p-LATS1 / LATS1, and p-YAP / YAP proteins were significantly increased (P<0. 05) . Hippo-YAP signaling pathway inhibitor verteporfin reversed the improving effect of LID on ischemia-reperfusion injury in OLT rats (P<0. 05) . Conclusions LID may activate the Hippo-YAP pathway, which reduces the inflammatory response, oxidative stress, and liver cell apoptosis, and improves liver ischemia-reperfusion injury in OLT rats.