Objective To investigate the pathogenic bacteria characteristics of blood flow infection in children with hematologic neoplasms, thus providing an evidence for rational use of anti-infective drugs. Methods Retrospective analysis was performed on continuous children with hematologic neoplasms whose discharge diagnosis were sepsis/septic shock admitted to the Children's Hospital Affiliated to Soochow University from January 2021 to December 2021, and pathogen result and drug sensitivity data of bilateral blood culture examination before antibiotic use were collected. Results A total of 963 children with hematologic neoplasms were diagnosed with sepsis, with 141(14.6%) of positive blood culture, and 156 of pathogenic strains. The median age was 82 (31.5, 131) months, male/female: 2.05∶1. Gram-negative bacteria accounted for 43.59% in the positive blood culture group, and the top three were Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli. The susceptibility rate of piperacillin, tazobactam, cefepime and amiacamycin was all greater than 85%, and that to Imipenem to Pseudomonas aeruginosa was 50%, that to Meropenem to Pseudomonas aeruginosa was 56.25%, that to Imipenem and meropenem to Escherichia coli and Klebsiella pneumoniae was 93%. There were 5 strains of extended-spectrum-beta-lactamase(ESBL)-producing Klebsiella pneumoniae and 3 strains of Escherichia coli. Gram-positive bacteria accounted for 55.77%, the top three were Staphylococcus epidermidis, Staphylococcus hominis, and Streptococcus bradycosus. the susceptibility rates of Linezolid and Vancomycin were all 100%, whereas Fungi accounted for 0.64%. There were 109 cases of agranulocytosis among 141 children with positive blood culture, including 76 cases of post-chemotherapy myelosuppression, 42 cases of post-transplantation acquired immunodeficiency, 23 cases of marrow restoration. Totally 24 cases (17.02%) were septic shock and 15 cases (10.64%) were deaths. Conclusion Sepsis in children with hematologic neoplasms is more common in school-age children, with more boys than girls, and most of them occur in agranulocytosis. Although blood culture results show that Gram-positive bacteria is the main pathogenic bacteria, Gram-negative bacteria is the most important pathogenic bacteria causing death in children with sepsis. Gram-positive bacteria has highly sensitive to Vancomycin and Linezolid, similarly, Gram-negative bacteria has highly sensitive to Piperacillin, Tazobactam, Cefepime and Amikacin.