Abstract: OBJECTIVE To explore the clinical analysis of postoperative nosocomial infection of patients with lung cancer and the prevention effect of cefotaxime. METHODS The clinical data of 160 patients with lung cancer admitted and treated in the department of thoracic surgery from May 2014 to Oct. 2016 were collected. The incidence of postoperative nosocomial pulmonary infection was statistically analyzed. Univariate analysis and multivariate logistic regression analysis were performed to analyze the risk factors of infection. In the patients undergoing radical resection of lung cancer, 80 cases of patients were given 2 g of cefotaxime via intravenous drip in the perioperative period, and the rest 80 patients were given 4 g of cefotaxime via intravenous drip in the perioperative period. The postoperative pulmonary infection rate as well as the postoperative and preoperative hemoglobin, albumin levels in the blood and WBC count were compared between the two groups. RESULTS Of the 160 patients with lung cancer undergoing first operation, 47 cases of postoperative nosocomial pulmonary infection occurred, and the infection rate was 29.38%. Multivariate logistic regression analysis results showed that old age, diabetes history, COPD, smoking history, use time of acid-inhibiting agent, operation time, mechanical ventilation time, obvious incision pain were independent risk factors for postoperative nosocomial lung infection in lung cancer patients (P＜0.05). The postoperative levels of hemoglobin and albumin in two groups were significantly lower than before the operation, and the WBC counts were significantly higher than before the operation (P<0.001). The blood hemoglobin and albumin levels in the 4 g cefotaxime group were significantly higher than those of the 2 g cefotaxime group, and the WBC count in the 4 g cefotaxime group was significantly lower than that in the 2 g cefotaxime group (P<0.001). CONCLUSION There are a number of risk factors for postoperative nosocomial lung infection in patients with lung cancer. Prevention measures should be taken accordingly. Administration of small dose of cefotaxime during the perioperative period is effective in preventing postoperative infection.