Background and objective Cathepsin X (Cat X) has been identiifed as a member of cathepsin family. Studies have shown that Cat X is involved in tumorigenesis and tumor development of various cancers. hTe aim of this study is to investigate the relationship between the clinicopathological prognosis and the levels of Cat X and cystatin C in the serum of patients with lung cancer. Methods Blood samples were collected from 84 patients with lung cancer and 36 healthy control subjects. Cat X and cystatin C were determined by quantitative ELISA. Results Cat X and cystatin C levels were signiifcantly higher in the patients with lung cancer than that in the healthy control subjects (P<0.01). Cat X level was correlated with the pathological types of lung cancer (P=0.076). Cystatin C was positively correlated with TNM stage (P=0.01). Furthermore, cystatin C/Cat X was correlated with lymph node metastasis (P=0.058). hTe patients with high Cat X levels experienced sig-niifcantly shorter overall survival rates compared with those with low Cat X. Univariate analysis indicated that Cat X and TNM stage were related to overall survival. Multivariate Cox analysis indicated that TNM stage may be used as an independent prog-nostic variable in patients with lung cancer. Conclusion Cat X and cystatin C levels were signiifcantly higher in patients with lung cancer. Cat X and cystatin C detection in the sera may contribute to the diagnosis of lung cancer and may be used to evalu-ate the prognosis of patients with NSCLC.