Mechanical ventilation (MV) is a key means to maintain the life of patients with general anesthesia, and it is also an important measure of respiratory support treatment for critically ill patients, which saves the lives of many patients with severely impaired respiratory function. However, MV may also cause or aggravate lung injury, namely ventilator-induced lung injury (VILI). Tight junction protein plays an important role in mechanical ventilation-related lung injury, which affects the occurrence and development of lung injury by regulating the permeability of alveolar barrier and participating in inflammatory response. This article reviews the definition of VILI, the role of tight junction proteins in VILI, the mechanism of regulating tight junction proteins in VILI, and the treatment of VILI.