Background Recently, inflammation plays an essential role in the prognosis of atrial fibrillation (AF) patients. Systemic immune-inflammation index (SII), reflecting the inflammation status, which is measured by the formula: neutrophil count × platelet count/lymphocyte count, is a powerful prognostic marker in several types of cancer and cardiovascular disease. However, no information regarding the prognostic value of SII in patients with AF is available. Methods and results We retrospectively enrolled 1768 AF patients in our study. Demographic characteristics, laboratory data and echocardiography were measured and collected on admission. The primary endpoints were death from all causes and death from cardiovascular diseases. The secondary endpoints were major bleeding and stroke. During a mean follow-up of 22.35 months, 155 patients occurred death from all causes. For further analysis, patients were categorized into two groups according to the optimal cutoff value of SII level determined by using receiver operating characteristics curve analysis. The incidence of death from all causes and death from cardiovascular diseases in high SII group is significantly higher compared with that in low SII group. However, no significant differences were detected between two groups for the secondary endpoints (p>0.05). On multivariable Cox analysis with adjustment of potential confounders, the risk of death from all causes and death from cardiovascular diseases increased by 77.6% and 51.2%, respectively, in high SII group. Conclusion Systemic immune-inflammation index was significantly associated poor outcomes and was an independent predictor for mortality in atrial fibrillation patients.