Background: Interferon (IFN)-γ-inducible chemokines in the CXCR3/ligand axis are involved in cell-mediated immunity and play a significant role in the progression of cancer. Here we evaluate their clinical prognostic implications in patients with lung cancer. Methods: We enrolled patients with lung cancer (n = 144) and healthy volunteers as the controls (n = 140). Initial blood samples were collected and concentrations of IFN-γ and IFN-γ-inducible chemokines CXCL9, CXCL10, and CXCL11 were measured using ELISA. With regard to the various clinical parameters, intergroup comparisons were done using the measured marker levels, and the survival analysis was performed. Results: Of patients with lung cancer, 125 had non-small cell lung cancer (NSCLC), and 19 had small cell lung cancer (SCLC). Using receiver operating characteristic (ROC) analysis, the area under the curve (AUC) (95% CI) of CXCL9 was 0.83 (0.80 - 0.89) for differentiating lung cancer patients from controls. The levels of all the markers were not different among the pathologic cell types, and their levels were significantly higher in NSCLC patients with stage IV than in those with stages I - III. A Kaplan-Meier survival analysis showed that NSCLC patients with higher levels of all markers showed poorer survival than those with lower levels. From the Cox multivariate analysis of NSCLC patients, CXCL9 and CXCL11 were found to be independent prognosticators for overall survival, and CXCL9 was also an independent prognosticator for cancer-specific survival. Conclusion: Serum IFN-γ-inducible chemokines may be useful as clinical markers for NSCLC. High levels of these chemokines are associated with metastasis and poor prognosis in patients with NSCLC, and CXCL9 levels showed the most significant results.