To identify a proliferation-inducing ligand (APRIL) expression profile in tumor tissue and sputum of lung cancer, and evaluate the possibility of an assistant diagnosis of lung cancer by real-time fluorescence quantitative polymerase chain reaction (RTQ-PCR) in sputum as well, the authors analyzed the expression of APRIL mRNA in 75 tissue samples and 71 corresponding sputum samples of lung cancer by RTQ-PCR and analyzed their correlation. APRIL protein expression was also observed in tumor tissues by Western blot and immunohistochemistry. The expression analysis revealed APRIL expression was elevated in non-small cell lung cancer (NSCLC) and the expression of APRIL protein was located in the membrane and cytoplasm of tumor cells by immunohistochemiscal staining. Compared to benign pulmonary disease and healthy volunteers, the expression of APRIL mRNA in sputum of lung cancer was elevated (both P <. 001). When cut-off values for positivity were set at the mean + 2SD of mRNA expression in healthy volunteers, the positive rate for APRIL mRNA expression was 81.7% (58/71) in sputum samples of lung cancer, 3.2% (2/62) in benign pulmonary disease, and 1.5% (1/65) in healthy volunteers. The correlation was evident between the expression level of APRIL mRNA of tissue samples and that of sputum samples (P <. 001, r =. 702). These results support the possibility that the APRIL gene may play a key role in lung cancer, especially in NSCLC. The elevated expression level of APRIL mRNA in sputum of NSCLC suggested that APRIL mRNA may serve as an effective and convenient diagnostic biomarker for NSCLC.