H19 and miR-21 expression was measured in tumor tissues and corresponding non-tumor lung tissues from 200 patients by quantitative reverse transcription polymerase chain reaction. Expression of both H19 and miR-21 was significantly higher in lung tissues from patients with NSCLC than in normal lung tissues. Increased expression of H19 and miR-21 was positively correlated with advanced tumor-node-metastasis stage and tumor size. miR-21 expression was highest in stage I and II NSCLC, whereas H19 expression was highest in stage III and IV NSCLC. The results show that H19 may mainly contributes to the progression of NSCLC, and its expression levels can reflect the invasive and metastatic status to some extent. New H19 and miR-targeting anticancer drugs will soon enter the clinical stage of development and ultimately become available for the treatment of patients with lung cancer.