The study evaluated the role of systemic immune inflammation index (SII) in differentiating juvenile idiopathic arthritis (JIA) from reactive arthritis (ReA) in Chinese children under 18 years of age. They retrospectively analyzed 865 patients and found that SII had higher diagnostic accuracy (AUC = 0.83) for distinguishing JIA from ReA compared with CRP (AUC = 0.81), ESR (AUC = 0.78), and hemoglobin (AUC = 0.75). The DeLong statistical test confirmed that SII is a significantly better predictor than other markers (p < 0.05). Independent risk factors for JIA include joint type, red blood cell distribution width (RDW), neutrophil count, platelet count, SII, platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR). Conversely, hemoglobin, lymphocyte count and some other hematological parameters act as protective factors. SII correlates with inflammatory cells, particularly neutrophils, platelets, and lymphocytes, with these correlations being stronger in patients with JIA. Higher SII values are associated with disease activity and may serve for early differential diagnosis between JIA and ReA.