Objective To explore the effects of intravenous lidocaine infusion on intrapulmonary shunt and inflammatory response in patients with one‑lung ventilation (OLV) undergoing thoracoscopic surgery. Methods According to random number table method, sixty patients who underwent thoracoscopic pulmonary surgery under elective general anesthesia were divided into the lidocaine group (group L) and the control group (group C), with 30 cases in each group. While other anesthetics used in patients of the two groups are all the same, the patients in group L received lidocaine 1.5 mg/kg intravenously, followed by a continuous infusion of 1.5 mg·kg−1·h−1, and group C received an intravenous injection of the same amount of normal saline. Records of two groups of patients with general information and intraoperative situation. Heart rate, mean artery pressure (MAP) before tracheal intubation, 1 min after intubation, and immediately after extubation of patients in two groups were recorded. Heart rate, MAP, hemoglobin (Hb), partial pressure of oxygen (PaO2), and the pressure of carbon dioxide (PaCO2) of patients were recorded at the time of two‑lung ventilation (T0), 15 min of OLV (T1), 30 min of OLV (T2), and the intrapulmonary shunt rate was calculated. Serum interleukin (IL)‑6, IL‑8, tumor necrosis factor‑α (TNF‑α) levels were detected at T0 and the end of surgery (T3). Results Compared with before tracheal intubation, the MAP and heart rate of patients in the two groups increased 1 min after intubation and immediately after extubation (P<0.05). The MAP and heart rate of group L are lower at 1 min after intubation and immediately after extubation than the parameters in group C (P<0.05). Compared with T0, the levels of IL‑6, IL‑8 and TNF‑α in the two groups were increased at T3 (P<0.05). The levels of IL‑6, IL‑8 and TNF‑α in group L were lower at T3 than the levels of the group C (P<0.05). There was no significant difference in PaO2, PaCO2, intrapulmonary shunt rate, Hb, MAP and heart rate between the two groups at each time point (P>0.05). Compared with T0, the intrapulmonary shunt rate increased, and PaO2 decreased at T1 and T2 in both groups (P<0.05). Conclusions Intravenous infusion of lidocaine can effectively inhibit the stress response during double‑lumen bronchial intubation and extubation, reduce the release of inflammatory factors during surgery, and has no significant effect on intrapulmonary shunt in patients with OLV.