Aims: To investigate the diagnostic value of lung-specific X protein (LUNX) messenger ribonucleic acid (mRNA) expression in peripheral blood of patients with nonsmall cell lung cancer (NSCLC) in micrometastasis. Materials and Methods: Peripheral blood samples of 112 patients with NSCLC were collected, and the expression of LUNX, cytokeratin 19 (CK19), and carcinoembryonic antigen (CEA) mRNA was measured by reverse transcription-polymerase chain reaction (RT-PCR). Results: The expression of LUNX, CK19, and CEA mRNA was increased in peripheral blood of patients with NSCLC compared with that of patients with benign lung disease (P < 0.05), and the sensitivity of LUNX mRNA was higher than that of CK19 and CEA mRNA (P < 0.05). LUNX-positive expression was also associated with lymph node metastasis, tumor-node-metastasis (TNM) staging, and reduced 5-year survival rate of patients in our cohort (P < 0.05). Further, the 5-year survival improved for those LUNX-positive patients who became LUNX negative following adjuvant chemotherapy compared to those who remain LUNX positive (P < 0.05). Multivariate analysis showed that lymph node metastasis, TNM stage, and LUNX mRNA expression in peripheral blood were independent prognostic factors. Conclusion: The detection of LUNX expression in peripheral blood of patients with NSCLC by RT-PCR is a highly specific and sensitive detection method for tumor micrometastasis that may be used for molecular diagnosis of tumor micrometastasis. LUNX mRNA expression in peripheral blood is an independent factor affecting prognosis of NSCLC and thus may reliably predict NSCLC prognosis and guide appropriate adjuvant chemotherapy treatment.