Abstract: Objective To discuss the use of limb ischemic preconditioning before hepatectomy and hepatic portal ischemic preconditioning during surgery to induce autophagy signals, so as to relieve liver ischemia reperfusion (IR) injury in patients with hepatectomy. Methods A total of 160 hepatic cell cancer patients who underwent hepatectomy from June 2016 to June 2019 were enrolled. They were divided into the following groups (n=40). A control group underwent hepatectomy; a test group 1 received limb ischemia preconditioning and hepatectomy; a test group 2 received hepatic portal ischemic preconditioning and hepatectomy; and a test group 3 received limb ischemia preconditioning, hepatic portal ischemic preconditioning and hepatectomy. Their liver injury was monitored, the levels of autophagy and apoptotic protein in liver tissue were detected, and their intraoperative condition, postoperative complication rate and the length of hospitalization stay were compared. Results The values of liver function in the test groups were lower than that in the control group, and the values in the test group 3 was significantly lower than those in the test groups 1 and 2. The levels of autophagy protein was more higher in the test groups than those in the control group, and the levels in the test group 3 was significantly lower than those in the test groups 1 and 2. Furthermore, the levels of apoptotic protein in the test groups was lower than that in the control group, and the levels in the test group 3 was significantly lower than those in the test groups 1 and 2. Liver HE staining showed various degrees of necrosis and fatty degeneration in the test groups, where the liver HE staining scores was lower in the test group 3 than those in the test groups 1 and 2. No significant difference was found in intraoperative conditions among the four groups. The test groups presented remarkably shorter length of hospitalization stay than the control group, without statistical difference among the test groups. The test groups presented remarkably better postoperative complication rate than the control group, without statistical difference among the test groups. Conclusions The combine use of ischemic preconditioning and hepatic portal ischemic preconditioning before surgery can induce autophagy signals to alleviate liver ischemic perfusion injury in patients with hepatectomy. Such combination can produced stronger effects on relieving liver injury than limb ischemic preconditioning and hepatic portal ischemia preconditioning alone, which provides new thoughts for relieving liver injury in patients with hepatectomy.