Objective To understand the clinical manifestations and epidemiological characteristics of hospitalized cases of hemorrhagic fever with renal syndrome in Guangzhou, analyze the influencing factors of patients with severe illness, and provide scientific basis for deepening disease recognition and identifying severe illness. Methods A retrospective selection of 572 patients with a clear diagnosis of hemorrhagic fever with renal syndrome who were hospitalized in second-level and higher medical institutions in Guangzhou since January 2014 were selected as the research objects. Questionnaires were designed and the epidemiological history clinical manifestations and laboratory test results of patients were collected. Multivariate logistic regression analysis was used to identify the influencing factors of patients with severe HFRS. Results Among the 572 patients, there were 406 males and 166 females. The male-to-female ratio was 2.45:1. The youngest was 14 years old, the oldest was 89 years old, and the average age was (41.21±14.16)years old. The clinical manifestations were mainly fever, acute onset, and fatigue, which accounted for 96.33%, 88.29% and 82.32%. There were 93 severe cases with a severe rate of 16.26%. Different neck redness, chest redness, abdominal pain, diarrhea, nausea, and nausea, vomiting, eyelid edema, jaundice, oliguria or anuria, hypotension, shock, decreased white blood cell count, urine membranes and rodent exposure, there were statistically significant differences in the incidence of severe illness (all P<0.05). The logistic regression analysis of factors showed that the age of 40-49 years, vomiting, shock, the presence of rats in the room, and food without rodent-proof equipment were risk factors for severe illness. The OR values and 95%CI were 2.712 (95 %CI: 1.039-7.077), 2.99 (95%CI: 1.462-6.114), 5.822 (95%CI: 1.891-17.927) and 3.292 (95%CI: 1.479-7.327). Conclusion Patients with clinical manifestations of vomiting and shock symptoms and a clear history of rodent exposure are at higher risk of severe illness. In the future prevention and treatment, health promotion and education should be further strengthened, rodent control activities should be carried out extensively, and early intervention is taken clinically to improve the patient's healing effect.