Abstract: Objective To explore the clinical characteristics of nosocomial septicemia in the early stage after hematopoietic stem cell transplantation (HSCT) in children with major β-thalassemia. Methods The clinical data were retrospectively analyzed of 55 consecutive children with major β-thalassemia who developed septicemia early after HSCT between January, 2011 and June, 2016. Results Among the total of 416 consecutive children with major β-thalassemia undergoing allogeneic HSCT, the incidence of nosocomial infection early after transplantation was 77.16% (321/416), and 55 (17.13%) children showed positive findings in blood culture test. The infections occurred most commonly in the oral cavity (65.5%), followed by the respiratory tract, intestinal tract and skin. Gram-negative bacteria, including Escherichia coli (27.3%), Klebsiella pneumoniae (21.8%) and Pseudomonas aeruginosa (9.1% ), were the most common causes of infections. Fungal (Candida tropicalis) infection caused septicemia in 1 case. Of all the pathogens, extended-spectrum β-lactamase (ESBL)-producing bacteria were found in 6 cases, methicillin-resistant Staphylococcus aureus (MRSA) in 2 cases, and multidrug-resistant (MDR) bacteria in 2 cases. Conclusion Gram-negative bacteria are the major pathogens causing septicemia in children early after HSCT for major β-thalassemia, and the bacteria show a high level of drug resistance. Adequate preventive use of antibiotics and care of the oral cavity, the respiratory tract, and the perianal region following the transplantation are important measures to control nosoconial infection in these children.