Objective To explore the current situation and characteristics of blood-borne occupational exposure among healthcare workers (HCWs) in emergency department, provide evidence-based support for the construction of scientific occupational protection system. Methods Data of blood-borne occupational exposure cases reported by the emergency departments of two tertiary hospitals in Guangdong Province from January 2021 to December 2024 were systematically analyzed by retrospective survey. Results A total of 52 cases of blood-borne occupational exposure incidents among HCWs in emergency departments were included in analysis, with nursing staff taking the highest proportion (67.31%), followed by doctors (23.08%). 78.85% of the exposed individuals have worked for ≤5 years, exhibiting a junior staff clustering feature. Distribution of exposure time showed that the third quarter was a high-incidence period, with sharp device injuries being the major exposure mode (94.23%). The high-risk links concentrated in needle withdrawal (23.08%), sharp device disposal (17.31%), medical waste disposal (15.38%), and suturing procedures (15.38%). Among the 52 cases, 7 cases were positive for blood-borne pathogens, with a positive rate of 13.46%. Hepatitis B virus (HBV) was the most commonly exposed pathogen (n=4, including 1 case of mixed infection). 45 cases underwent quantitative detection of hepatitis B surface antibodies (anti-HBs), with 5 cases (11.11%) <10 IU/L, 10 cases (22.22%) between 10-100 IU/L, and 30 cases (66.67%)>100 IU/L. The average prevention and control cost for blood-borne occupational exposure was 366.47 Yuan per case. Conclusion Blood-borne occupational exposure in the emergency department mainly occurs among junior HCWs and was mainly due to sharp device injuries. It is necessary to establish protective training system for high-risk populations, with a focus on strengthening safety injection and occupational safety training to reduce occupational exposure risk.