The identification of cancer-associated long non-coding RNAs (LncRNA) and the investigation of their molecular and biological functions are important for understanding the molecular biology and progression of cancer. This study aims to find the key LncRNA associated with lung adenocarcinoma and to evaluate its biological role and clinical significance in tumor progression. Microarray analysis of 32,756 LncRNA was performed to screen the significantly different LncRNA between human lung adenocarcinoma tissues and adjacent non-cancerous lung tissues, which was named as LncRNA ZXF1. Expression of LncRNA ZXF1 was analyzed in 62 lung adenocarcinoma tissues and adjacent non-cancerous lung tissues by quantitative reverse-transcription PCR (qRT-PCR). Correlations between LncRNA ZXF1 expression and the clinicopathological features and prognosis of patients were also analyzed. The inhibition of LncRNA ZXF1 using siRNA treatment was performed in order to explore its role in tumor progression. The effect of LncRNA ZXF1 on proliferation was evaluated by CCK-8 assay using A549 cell lines, and cell migration and invasion were detected by transwell assays. Here we found that LncRNA ZXF1 levels were remarkably increased in lung adenocarcinoma tissues compared with adjacent non-cancerous lung tissues (P<0.05), and up-regulated LncRNA ZXF1 was correlated with lymph node metastasis (P<0.05), tumor pathological stage (P<0.05) and the extent of lymph node metastasis (correlation coefficient=0.366). The 3-year overall survival rate of patients with higher LncRNA ZXF1 levels was remarkably reduced compared with patients with lower LncRNA ZXF1 levels, implying that patients with high levels of LncRNA ZXF1expression had a relatively poor prognosis. Inhibition of LncRNA ZXF1 by siRNA decreased the migration and invasion of A549 cells in vitro, while there was no significant effect in cell proliferation.