Objective To investigate the clinical significance of serum cystatin C ( Cys C) in patients with non-small cell lung cancer ( NSCLC) .Methods The serumlevel of cystatin C was determined by enzyme linked immunosorbent assay ( ELISA) in patients with NSCLC, patients with benign lung diseases, and normal controls. Results The serum level of Cys C in the NSCLC patients was much higher than those in the patients with benign lung diseases and the normal control subjects [ ( 1.47 ±0.78) mg/L vs. ( 1.04 ±0.51) mg/L and ( 1.06 ±0.36) mg/L, Plt;0.01] . The level of Cys C in the NSCLC patients was significantly related to clinical stage [ TNM stage -Ⅱ vs. Ⅲ-Ⅳ: ( 1.38 ±0.88) mg/L vs. ( 1.57 ± 0.79) mg/L] , lymph node metastasis [ metastatic vs. non-metastatic: ( 1.83 ±0.97) mg/L vs. ( 1.06 ± 0.39) mg/L] , and differentiation degree [ medium-high differentiation vs. low differentiation: ( 1.63 ± 0.73) mg/L vs. ( 1.26 ±0.48) mg/L] ( all Plt;0.05) . However no correlation of Cys C with gender, age, and histological type was revealed ( Pgt;0.05) . Conclusion Cys C may contribute to the occurrence and development of NSCLC.