To investigate whether the soluble Klotho (s-Klotho) level in patients with chronic kidney disease (CKD) is related to kidney function and whether a low s-Klotho level can predict adverse renal outcomes or CKD progression in patients with advanced CKD. 112 patients with CKD stages 3–5 and 30 healthy volunteers were enrolled. Blood samples were collected to measure serum creatinine, calcium, phosphorus, intact parathyroid hormone, and hemoglobin. s-Klotho and fibroblast growth factor 23 (FGF23) were determined by ELISA. We first conducted a cross-sectional study to investigate correlations between s-Klotho and estimated glomerular filtration rate (eGFR) and other parameters. Patients were then followed prospectively for 20.1±10.1 months according to s-Klotho median level until serum creatinine doubled, or initiation of renal replacement therapy, or death. s-Klotho levels inpatients with CKD were significantly lower than that in the control group. For patients with CKD, there were no differences in age distribution among subgroups. However, s-Klotho level differed significantly across CKD stages, and it was lower in the advanced CKD group compared with the moderate CKD group. Correlation analysis revealed that s-Klotho was positively associated with eGFR, but inversely associated with FGF23. During the follow-up of 20.1±10.1 months, patients with higher s-Klotho levels showed a reduced risk of kidney adverse outcomes, including serum creatinine doubling and initiation of renal replacement therapy. Cox regression analysis revealed that low s-Klotho was an independent risk factor for CKD progression. s-Klotho level was closely correlated with kidney function, further, low s-Klotho level could predict adverse kidney disease outcomes in patients with progressive CKD.