Abstract: OBJECTIVE To investigate the correlation between serum levels of 5 commonly used lung cancer biomarkers squamous cell carcinoma antigen（SCC）, carcinoembryonic antigen（CEA）, soluble cytokeratin 19 fragment（Cyfra21-1）, neuron-specific enolase（NSE）, pro-gastrin releasing peptide（proGRP） and the severity and clinical outcome of sepsis. METHODS A total of 88 patients with sepsis hospitalized in the internal intensive care unit（ICU） of Peking University Third Hospital from Jan 2016 to Dec 2019 were selected. The correlations between the lung cancer markers and the SOFA score, and APACHE II score were analyzed. Prognosis risk biomarker score was established according to the levels of the five serum lung cancer biomarkers. RESULTS Septic shock accounted for 23.9% of 88 sepsis patients, and the hospital mortality was 35.2%. Patients with increased serum levels of SCC, CEA, Cyfra21-1, NSE and proGRP accounted for 72.9%, 53.2%, 73.2%, 51.9%, and 36.2% patients, respectively. Multivariate Logistic regression analysis showed that the SOFA score（OR=1.435, P=0.020）, prognosis risk biomarker score（OR=3.336, P=0.045） and age（OR= 1.115, P= 0.045） were independent risk factors for hospitalized mortality of sepsis patients. CONCLUSION The levels of serum lung cancer markers were elevated in more than half of the patients with sepsis, which were related to the severity of the disease. The prognosis risk biomarker score was one of the independent risk factors for hospitalized mortality of sepsis patients.