Abstract: Objective To investigate the etiological characteristics of nosocomial infection in patients with acute leukemia and the expression of hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF) and B cell lymphoma/leukemia-2 (Bcl-2) in the bone marrow tissues of acute leukemia patients. Methods Total 171 cases of acute leukemia treated in our hospital between January 2014 and December 2017 were selected, and the incidence of nosocomial infection, the distribution of pathogenic bacteria and the drug resistance of the main pathogens were analyzed. The pathological sections of the bone marrow were taken for immunohistochemical staining to detect the expressions of HIF-1α, VEGF and Bcl-2, and the mean optical density was used for quantitative analysis. Results Among the 171 patients, 54 cases had nosocomial infection, with a rate of 31.58%. Of the 54 nosocomial infections, respiratory tract, oral cavity and gastrointestinal tract were the main type of infections, accounting for 35.19%, 24.07% and 16.67%, respectively; There were 71 strains of pathogenic bacteria isolated from 54 patients with nosocomial infection, including 39 strains of Gram-negative bacteria (54.93%), 15 strains of Klebsiella pneumoniae (21.13%), 12 strains of Staphylococcus aureus (16.90%), 10 strains of Pseudomonas aeruginosa (14.08%) and 9 strains of coagulase-negative Staphylococcus (12.68%). Among the main gram-negative bacteria, Klebsiella pneumoniae had a high resistance rate to cefoperazone (53.33%) and Pseudomonas aeruginosa had a high resistance rate to piperacillin (60.00%). Among the Gram-positive bacteria, Staphylococcus aureus had a high resistance rate to erythromycin (75.00%) and coagulase-negative Staphylococcus had a high resistance rate to erythromycin (66.67%). The average optical density of HIF-1α and VEGF in bone marrow tissue of the infected group was higher than that of the uninfected group, while the average optical density of Bcl-2 was lower than that of the uninfected group (all P < 0.05). Conclusion The incidence of nosocomial infection in patients with acute leukemia is high.The pathogenic bacteria are mainly Gram-negative bacteria, and HIF-1α, VEGF and Bcl-2 are highly expressed in the bone marrow tissues of the infected patients, which is of great significance.