Abstract: OBJECTIVE To screen out accurate and reliable peripheral blood biomarkers for severe pulmonary infection with respiratory failure, and analyze their prognostic value. METHODS A total of 117 patients with severe pulmonary infection and respiratory failure admitted to the hospital from Jan. 2019 to Dec. 2020 were selected and divided into 84 cases of survival group and 33 cases of death group according to the 28-day prognosis. The results of the related indicators of venous blood was analyzed after transfer to intensive care unit（ICU）. RESULTS The levels of IL-6, PCT, ESR, SAA, D-D, Cr, BUN, NT-proBNP, MIP-2, MPO, HMGB1 and S100-β in the death group were significantly higher than those in the survival group（P＜0.05）. Logistic regression analysis showed that IL-6, PCT, D-D, BUN, NT-proBNP, HMGB1 and S100-β were influencing factors in evaluating prognosis. Receiver operating characteristic curve（ROC） analysis showed that the area under curve for the above indicators to evaluate prognosis was 0.706, 0.722, 0.728, 0.784, 0.682, 0.707, and 0.741, respectively. BUN had the highest sensitivity, which was 84.52%, and HMGB with the highest specificity, which was 78.79%. CONCLUSION Totally 7 valuable peripheral blood biomarkers were screened for the prognosis of severe pulmonary infection combined with respiratory failure, namely IL-6, PCT, D-D, BUN, NT-proBNP, HMGB1, and S100-β.