Trichloroethylene (TCE) is a common industrial organic solvent and environmental contaminant. People are exposed to TCE through occupational contact or environmental pollution, which leads to serious human health hazards. A large number of studies have shown that oxidative stress plays an important role in the TCE-induced multi-target organ toxicity. However, the research of related signaling pathways remains to be deepened. In this review, we summarized the epidemiological, animal, and cellular studies correlated to liver toxicity, kidney toxicity, cardiac developmental toxicity, placental developmental toxicity, neurodevelopmental toxicity, and autoimmune response induced by TCE. In addition, the possible molecular mechanisms of oxidative stress in TCE-induced toxicity were concluded, including DNA damage, mitochondrial dysfunction, cell apoptosis, and abnormal activation of the immune system. Through literature review, we proposed that nuclear factor E2 related factor 2 may play an important role in mediating TCE-induced target organ toxicity, providing a theoretical basis for the prevention and treatment of adverse health effects caused by TCE.