Objective Both cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) are markers of kidney injury and may also be marker candidates for neuroinflammation. The aim of this article is to explore the relationship between kidney injury and ischemic stroke (IS).Methods 498 IS patients were enrolled, and 173 IS-related disease control (DC) patients and 293 healthy control (HC) subjects were randomly selected. We analyzed the relationship between the levels of serum kidney function markers (including NGAL, Cre, Ure, CysC and eGFR) and the occurrence of IS.Results When they were admitted to the hospital, the NGAL level of patients with first-onset IS was higher than that of both HC group (z=5.964, P<0.001) and DC (z=12.191, P<0.001); The level of CysC of them was higher than that of HC group (z=5.762, P<0.001), and was the similar with that of DC group (z=1.663, P=0.289). The partial correlation coefficient between NGAL and the occurrence of IS was the highest (rp=0.341, P<0.001) in IS patients with normal kidney function. However, the partial correlation coefficient between CysC and IS was the highest (rp=0.460) , P<0.001) in IS patients with chronic kidney disease (CKD). For patients with normal kidney function, only NGAL was a risk factor for IS [OR(95%CI)=6.54(3.75,11.41)], and had the certain predictive performance AUC=0.734(z=12.928, P<0.001). However, for CKD patients, CysC has better predictive performance for IS occurrence AUC=0.835 (z=11.343, P<0.001) and risk assessment ability [OR(95%CI)=5.97(2.45, 14.56)] than NGAL.Conclusion IS is related to kidney injury and neuroinflammation. NGAL and CysC are suitable for IS prediction in patients with normal kidney function and CKD, respectively. Researchers should pay attention to the changes of NGAL and CysC for the prevention and treatment of stroke in these two types of patients, respectively.