N-Myc downstream-regulated gene 2 (NDRG2) has been demonstrated to influence the metastatic potential of hepatocellular carcinoma and breast cancer cells by regulating CD24 expression. The aim of this study was to investigate the roles of NDRG2 and CD24 in the clinical pathology of lung adenocarcinoma and to explore whether the expression of these two markers can be used as independent factors for the prediction of prognosis in patients with this tumor. NDRG2 and CD24 expression in paraffin-embedded specimens gathered from 166 patients with lung adenocarcinoma was detected by immunohistochemical method. The correlation of these two proteins expression with clinicopathological parameters and prognosis was statistically analyzed. NDRG2 and CD24 proteins were highly expressed in 59/166 (35.5 %) and 110/166 (66.3 %) of lung adenocarcinoma patients, respectively. High expression of NDRG2 was frequently found in lung adenocarcinoma tissues in early pTNM stage (p = 0.01) and without pathological metastasis (p = 0.02), whereas the high expression of CD24 was significantly associated with the advanced pTNM stage (p = 0.04) and pathological metastasis (p = 0.01). Univariate analysis indicated that the patients with NDRG2 high expression correlated with favorable prognosis in patients with lung adenocarcinoma (p = 0.001), as opposed to CD24 (p = 0.001). The survival rate of the patients with NDRG2-low/CD24-high expression was the lowest (p < 0.001). Multivariate statistical analysis showed that the conjoined expressions of NDRG2-high/CD24-low and NDRG2-low/CD24-high were independent prognostic indicators of lung adenocarcinoma (p = 0.03 and p = 0.02, respectively). Our results suggest that the decreased expression of NDRG2 or the increased expression of CD24 is an important feature of lung adenocarcinoma. A combined detection of NDRG2/CD24 co-expression may benefit us in prediction of the prognosis of lung adenocarcinoma.