Aim: The study aimed to investigate and compare the predictive capacity of a systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to determine a hemodynamically significant coronary artery stenosis assessed by fractional flow reserve (FFR). Patients & methods: A total of 207 chronic coronary syndrome patients with FFR measurement were enrolled in the study. NLR, PLR and SII levels were calculated. Results: The cut-off value of the SII (620) was associated with 78.4% sensitivity and 64.0% specificity to predict a hemodynamically significant stenosis. SII level independently predicted FFR <= 0.80. Conclusion: SII is an independent predictor of functionally significant coronary stenosis detected by FFR in chronic coronary syndrome patients. SII levels can predict hemodynamically severe obstruction better than NLR and PLR.