Background and Aims. Midkine (MDK) is a heparin-binding growth factor and is over expressed in various types of human cancer. However, little is known about the clinical significance of MDK in non-small cell lung cancer (NSCLC). The aim of this study was to measure MDK protein levels in patients with NSCLC and to explore its clinical significance. Methods. The expression status of MDK in NSCLC at Gene Expression Omnibus (GEO accession number: GSE19804) was observed. The expression of MDK mRNA and protein was examined in NSCLC tissues and normal lung tissues through real-time PCR and Western blot. Meanwhile, the relationship of MDK protein expression levels with clinical characteristics of 186 NSCLC patients was analyzed by immunohistochemistry. Results. MDK expression was increased in NSCLC tissues compared with paired normal lung tissues in microarray data (GSE19804). MDK mRNA and protein expression were obviously increased in NSCLC tissues than in paired adjacent normal lung tissues. Using immunohistochemistry, MDK protein overexpression was positively correlated with status of clinical stage, T classification, N classification, and M classification in NSCLC patients. In survival analysis, patients with higher MDK protein expression had a significantly shorter overall survival time than did patients with lower MDK protein expression. Multivariate analysis indicated that the MDK protein overexpression was an independent poor prognostic indicator for patients with NSCLC. Conclusions. MDK plays an important role in NSCLC progression and prognosis and may act as a convincing prognostic indicator for NSCLC patients. (C) 2015 IMSS. Published by Elsevier Inc.