The first two authors contributed to the work equally.Yes-associated protein 1 (yAPl), a nuclear effector of the Hippo pathway, plays an important role in tumorigenesis and progression of multiple cancers. The present study aimed to investigate the clinical significance of YAPl and receptor tyrosine kinase Axl expression in human lung adenocarcinomas (LAC). We further explored possible molecular mechanisms mediated by YAPl in LAC and gastric adenocarcinoma (GAC) cells. Forty-nine cases of human LAC and normal lung tissue (NLT) were collected. The expression of YAPl and Axl was assessed by immunohistochemical assay through tissue micro array procedure and the clinicopathologic characteristics of all patients were analyzed. Using a loss of function approach, we investigated the effects of small hairpin RNA (shRNA)-mediated knockdown of YAPl on the expression of Axl, proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-9 (MMP-9), and the proliferative activities and invasive potential in LAC A549 and GAC SGC-790l cell lines. As a result, the expression of YAPl and Axl was found in LAC tissues with higher strong reactivity rate compared to the NLT (87.8% vs.60.8%, p=0.000; 77.6% vs 0.0%, P=O.OOO), but they did not associate with the age, gender, tumor size, TNM staging or lymph node metastases of LAC patients (each P>0.05). Spearman rank correlation analysis showed a positive correlation between YAPl and Axl expression. Furthermore, knockdown of YAP in vitro markedly down-regulated the expression of AxI, PCNA and MMP-9, and inhibited the proliferation and invasion of LAC and GAC cells. Taken together, YAPl and Axl are highly expressed in LAC compared to the NLT, and knockdown of YAPl may inhibit the proliferation and invasion of adenocarcinoma cells through downregulation of the Axl pathway, representing a potential therapeutic target for the treatment of cancer.Lung cancer was the most commonly diagnosed cancer and leading cause of cancer death in males worldwide in 2008. Among females, it was the fourth most commonly diagnosed cancer and the second leading cause ofcancer death (l). The current best approach for treatment of cancer is complete surgical removal of the tumor and adjacent lymph nodes. However, the efficacy of this therapeutic approach alongside hormone, radio, and chemotherapy is very limited (2,3). Cancer is also a genetic disease that develops from a multi-step process. Single or multiple mutations in genes related to growth control, invasion, and metastasis form the molecular genetic basis of malignant transformation