Objective:To investigate the risk factors of moderate to severe pain in patients with non-small cell lung cancer within 3 days after lobectomy.Methods:The clinical data of 297 patients with non-small cell lung cancer who underwent lobectomy in the Department of Thoracic Surgery, Sun Yat-sen University Cancer Center from December 2020 to June 2021 were retrospectively analyzed. A numerical rating scale was used to score the most severe pain within 3 days after surgery. Pain score ≥ 4 was defined as moderate to severe pain. The risk factors for moderate to severe pain were analyzed by binary Logistic regression. General linear model repeated measures and linear mixed models were used to analyze the trend of risk factors influencing postoperative pain with time.Results:The incidence of moderate to severe pain was 34.2% (102/297), 59.8% (178/297), 66.4% (198/297), and 28.2% (84/297) on days 0, 1, 2, and 3 after surgery respectively. The risk for moderate to severe pain was significantly higher in patients undergoing thoracotomy than patients undergoing thoracoscopic surgery on days 1 ( OR = 1.99, P = 0.009), 2 ( OR = 3.08, P < 0.001), and 3 ( OR = 3.88, P < 0.001) after surgery. However, the risk for moderate to severe pain in patients undergoing thoracotomy was slightly, but not significantly, higher than that in patients undergoing thoracoscopic surgery ( OR = 1.53, P = 0.087). The risk for moderate to severe pain was higher in female patients than male patients on day 2 ( OR = 1.62, P = 0.077), and in particular on day 3 after surgery ( OR = 2.39, P = 0.002). Prophylactic use of parecoxib significantly reduced the risk of moderate to severe pain on day 0 ( OR = 0.32, P = 0.004), 1 ( OR = 0.20, P < 0.001), 2 ( OR = 0.36, P < 0.001) and 3 ( OR = 0.56, P = 0.047). Conclusion:The incidence of moderate to severe pain on days 1 and 2 after lobectomy was relatively high in patients with non-small cell lung cancer. Patients undergoing thoracotomy have a higher risk of moderate to severe pain than those who underwent thoracoscopic surgery. Female patients have a higher risk for moderate to severe pain on days 2 and 3 after surgery than male patients. Prophylactic use of parecoxib can decrease the risk for moderate to severe pain in patients with non-small cell lung cancer.