The application of tourniquet in lower limb surgery can cause iatrogenic ischemia-reperfusion injury (IRI), and the consequent damage to distal organ function is highly emphasized in the research of perioperative organ protection. There have been extensive basic and clinical studies focusing on the effect of iatrogenic IRI of lower extremity on essential remote organs, such as the heart, lungs, liver, kidneys and brain. Despite the diversity of distal organs affected by the IRI of lower extremity, the critical injury mechanisms are roughly the same, mainly including the accumulation of neutrophils, the generation of oxygen free radicals, the calcium overload, the alteration of cell membrane permeability, and the activation of inflammatory mediators along with the cascade reactions. The clarification of the mechanisms of IRI of lower extremity may shed light on the potential organ targets or cell pathways for further researches on how to protect the organ function during the perioperative period.