This study investigated the effects of high-dose long-term antioxidant free radicals on the mortality rate, creatinine (Cr) value, partial pressure of oxygen (PaO2), alanine aminotransferase (ALT), as well as the incidence rates of lung fibrosis and dysfunction in the treatment of patients with severe paraquat (PQ) poisoning [toxic dose, 20 ml stock solution (20% w/v)]. A total of 23 cases of severe PQ poisoning treated in Xiangyang First People's Hospital, Hubei University of Medicine were collected (group 1), and they received conventional treatments such as immunosuppressive agents and/or hemoperfusion. Six patients were given high-dose long-term antioxidant therapy on the basis of conventional treatments (group 2). After treatment, 6 out of the 23 patients in group 1 survived, and all the 6 patients in group 2 survived, with the survival rate of 26.1 vs. 100% (p<0.01). The lowest PaO2 value in group 1 was lower than that in group 2 (70.26±16.38 vs. 91.17±3.43 mmHg, p<0.01). The highest ALT value in group 1 was higher than that in group 2 (216.74±126.23 vs. 52.50±24.83 U/l, p<0.01). There was no significant difference in the incidence rate of lung fibrosis between the two groups of survived patients, but there were 6 patients that died of severe lung fibrosis in group 1. Besides, the incidence rate of lung dysfunction in patients in group 2 was significantly lower than that in survived patients in group 1 (p<0.01). High-dose long-term antioxidants are the most critical treatment option to improve the survival rate of high-dose PQ poisoning, they increase the patient's PaO2, enhance liver function, reduce lung fibrosis and refine lung dysfunction.