Objective By analyzing the microbiology and risk factors for death of Gram-negative bacterial bloodstream infections (BSIs) in the general surgical intensive care unit (SICU), we provided a reference for the rational treatment of BSIs in this population. Methods Retrospective analysis of 122 cases of Gram-negative bacterial BSIs in SICU from January 2016 to December 2020 in the First Affiliated Hospital of Chongqing Medical University. Double-Disk Synergy Test confirmed the production of Extended Spectrum Beta-Lactamases (ESBLs). Modified Hodge Test confirmed carbapenem resistance. Binary logistic regression analysis was performed to find the risk factors affecting patient Death. All statistical analyses were done using SPSS 22.0.Results High rates of multi-drug resistance (MDR), septic shock, and mortality are manifested in the SICU population. The abdomen and lungs are the primary sources of secondary BSIs. Septic shock, prothrombin activity, and hypertension are independent risk factors for patient Death. Escherichia coli and Klebsiella pneumoniae are the primary clinical isolates and multi-drug resistant organisms (MDRO). Escherichia coli showed high resistance rates to antibacterial drugs other than amikacin, tigecycline, β-lactam/β-lactamase inhibitors, and carbapenems. In contrast, Klebsiella pneumoniae showed high resistance rates to common antibacterial drugs, with only tigecycline and minocycline being sensitive. Conclusion Patients with Gram-negative bacterial BSIs in the SICU are vulnerable to MDRO infections and septic shock with high mortality, the seriousness of which should be fully recognized. Active control of the source of infection, identification of risk factors, focused surveillance and response to Escherichia coli and Klebsiella pneumoniae and their resistant forms, and rational optimization of antimicrobial drug use are significant