Objective To investigate the pulmonary protective effects of butorphanol in patients undergoing thoracoscopic radical resection of lung cancer. Methods According to the random number table method, a total of 191 patients who were scheduled for thoracoscopic radical resection of lung cancer were divided into a butorphanol group (group B, n=95) and a control group (group C, n=96). After anesthesia induction, group B was intravenously injected with butorphanol at a loading dose of 10 μg/kg, followed by continuous pump infusion at 10 μg·kg−1·h−1 until the end of surgery, while group C was given the same volume of normal saline, meanwhile, other anesthetics used in both groups were the same. Their occurrence and severity of postoperative pulmonary complications (PPC) (pneumonia, atelectasis, pleural effusion, pneumothorax, respiratory failure and bronchospasm) within seven days after surgery were recorded. The partial pressure of oxygen in arterial blood (PaO2), oxygen index (OI), alveolar‐arterial oxygen difference (A‑aDO2), peak airway pressure (PIP), plateau pressure (Pplat) and dynamic lung compliance (Cdyn) were recorded before one‑lung ventilation (T1), after one‑lung ventilation for 30 min (T2), one‑lung ventilation for 60 min (T3) and total‑lung ventilation for 20 min (T4). The concentrations of Clara cell secretory protein (CC16), endothelin‑1 (ET‑1) and IL‑6 were measured before surgery (T0), at T1‒T4 and 24 h after surgery (T5). The Visual Analog Scale (VAS) scores at rest and on coughing were recorded at postoperative 6, 12, 24 h and 48 h. Furthermore, other perioperative indicators including surgery duration, OLV duration, extubation time, fluid volume, blood loss, the incidences of intraoperative hypoxemia and postoperative nausea and vomiting, the length of hospitalization stay, and intraoperative and postoperative opioid dosage) were recorded. Results Group B showed decreases in the incidence of atelectasis and the total incidence of PPC, and increases in the proportion of patients at PPC0.05). The plasma concentrations of CC16, ET‑1 and IL‑6 at T2‒T5 in both groups were higher than those at T0 (P<0.05). Compared with group C, the concentrations of CC16, ET‑1 and IL‑6 at T3‒T5 in group B decreased (P<0.05). Group B had lower VAS scores at rest and on coughing than group C at postoperative 6 h and 12 h (P<0.05). There was no statistical difference in VAS scores at rest and on coughing between both groups at postoperative 24 h and 48 h (P>0.05). Compared with group C, group B presented decreases in the intraoperative and postoperative opioid dosage (P<0.05), the incidence of nausea and vomiting (P<0.05) and the length of hospitalization (P<0.05). There was no statistical difference in surgery duration, one‑lung ventilation duration, extubation time, fluid volume, blood loss and the incidence of intraoperative hypoxemia (P>0.05). Conclusions For patients undergoing thoracoscopic radical resection of lung cancer, intravenous administration of butorphanol can improve perioperative oxygenation, reduce PPC within the first seven postoperative days, and then exhibit pulmonary protective effect.