BACKGROUND Thoracic surgery for radical resection of lung tumor requires deep anesthesia which can lead to an adverse inflammatory response, loss of hemodynamic stability, and decreased immune function. Herein, we evaluated the feasibility and benefits of ultrasound-guided paravertebral nerve block anesthesia, in combination with general anesthesia, for thoracic surgery for lung cancer. The block was performed by diffusion of anesthetic drugs along the paravertebral space to achieve unilateral multi-segment intercostal nerve and dorsal branch nerve block. AIM To evaluate the application of ultrasound-guided paravertebral nerve block anesthesia for lung cancer surgery to inform practice. METHODS The analysis was based on 140 patients who underwent thoracic surgery for lung cancer at our hospital between January 2018 and May 2020. Patients were randomly allocated to the peripheral + general anesthesia (observation) group (n = 74) or to the general anesthesia (control) group (n = 66). Patients in the observation group received ultrasound-guided paravertebral nerve block anesthesia combined with general anesthesia, with those in the control group receiving an epidural block combined with general anesthesia. Measured outcomes included the operative and anesthesia times, as well as the mean arterial pressure (MAP), heart rate (HR), and blood oxygen saturation (SpO(2)) measured before surgery, 15 min after anesthesia (T1), after intubation, 5 min after skin incision, and before extubation (T4). RESULTS The dose of intra-operative use of remifentanil and propofol and the postoperative use of sufentanil was lower in the observation group (1.48 +/- 0.43 mg, 760.50 +/- 92.28 mg, and 72.50 +/- 16.62 mg, respectively) than control group (P < 0.05). At the four time points of measurement (T1 through T4), MAP and HR values were higher in the observation than control group (MAP, 90.20 +/- 9.15 mmHg, 85.50 +/- 7.22 mmHg, 88.59 +/- 8.15 mmHg, and 90.02 +/- 10.02 mmHg, respectively; and HR, 72.39 +/- 8.22 beats/min, 69.03 +/- 9.03 beats/min, 70.12 +/- 8.11 beats/min, and 71.24 +/- 9.01 beats/min, respectively; P < 0.05). There was no difference in SpO, between the two groups (P > 0.05). Postoperative levels of epinephrine, norepinephrine, and dopamine used were significantly lower in the observation than control group (210.20 +/- 40.41 pg/mL, 230.30 +/- 65.58 pg/mL, and 54.49 +/- 13.32 pg/mL, respectively; P < 0.05). Similarly, the postoperative tumor necrosis factor-a and interleukin-6 levels were lower in the observation (2.43 +/- 0.44 pg/mL and 170.03 +/- 35.54 pg/mL, respectively) than control group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). CONCLUSION Ultrasound-guided paravertebral nerve block anesthesia improved the stress and hemodynamic response in patients undergoing thoracic surgery for lung cancer, with no increase in the rate of adverse events.