Low-grade inflammation is known to facilitate the development of hypertensive organ damage. The systemic immune-inflammation index (SII) is a new inflammatory index based on circulating immune-inflammatory cells. The objectives of this study were to investigate the relationship between the SII and asymptomatic organ damage (AOD) in patients with newly diagnosed treatment-naive hypertension (HTN). A total of 500 participants (≥ 18 years) were enrolled in the study, including 250 patients and 250 healthy volunteers. Microalbuminuria of > 30 mg/day or proteinuria of > 150 mg/day, left ventricular mass index of > 95 g/m2 in women and > 115 g/m2 in men, and carotid intima-media thickness of > 0.9 mm or the presence of plaque in the carotid were evaluated as AOD indicators. AOD grade was classified as follows: Grade I - One organ involved, Grade II - Two organs involved, Grade III - Three organs involved, and Grade IV - Four organs involved. SII values were higher among patients with HTN than in the control group. Positive correlations were found between the SII and AOD indicators and C-reactive protein levels. Increasing SII values were a common independent predictor of the presence and severity of AOD. The gradually increasing threshold values of the SII from no AOD to Grade III-IV exhibited high diagnostic performance. High SII values were independent predictors of the presence and severity of AOD in patients with newly diagnosed treatment-naive HTN. Considering the role of inflammation in HTN, the SII, which can be easily evaluated using blood parameters, can be an effective prognostic screening tool. (Rev Invest Clin. 2022;74(5):258-67).