To investigate the role of complement C5a in inflammatory cytokine storm of severe fever with thrombocytopenia syndrome (SFTS) and predict the severity of disease. Methods Patients with SFTS admitted from 2017 to 2021 were retrospectively analyzed, and their general clinical data and laboratory test indicators were analyzed. Pearson or Spearman correlation test was used to analyze the changes of complement C5a and laboratory test indicators, and continuous dynamic analysis (GEE) was used to analyze the changes of complement C5a. Area under the Receiver operating characteristic (ROC) curve was used to assess the effect of C5a on disease severity and prognosis. Results The level of complement C5a in the severe and critical groups was significantly higher than that in the general group (376.2±66.4, 404.2±75.3 vs 220.47±45.34), and there were a positive correlation between the complement C5a level and il-6 in SFTS patients (r=0.246, P=0.0024), a positively correlation with TNFα level (r=0.261, P=0.0017), and a positively correlation with severity score (r=0.4757, P＜0.001). According to the dynamic analysis of complement C5a, the complement C5a level of the normal group showed a dynamic balance, lower than the normal level, while the complement C5a level of the severe group showed a continuous downward trend, and the complement C5a level of the critically ill group remained high. The AUC curve area of complement C5a in predicting the severity of SFTS was 0.9332 (95% CI:0.8438-0.9692, P＜0.001), and the AUC curve area in predicting the prognosis of SFTS was 0.8946 (95% CI:0.8218-0.9341, P＜0.001). Conclusion Complement C5a is involved in the inflammatory factor storm of SFTS patients and can effectively predict the disease severity and prognosis of SFTS patients.