Objective To explore the role of Yes-associated protein 1 (YAP1) in the proliferation, cell cycle, migration and invasion of human non-small cell lung cancer (NSCLC) cells. Methods A lenti-siRNA targeting YAP1 (si-YAP1) was used to inhibit the expression of YAP1 gene of human NSCLC cell line A549 cells. CCK-8 assay and flow cytometry were used to determine the effects of silencing of YAP1 expression on A549 cells proliferation and cell cycle, respectively; Transwell assay was used to observe the effect of silencing of YAP1 expression on A549 cell migration and invasion. Results After infection with si-YAP1, the expressions of YAP1 mRNA and protein in A549 cells were significantly down-regulated (P<0.01). YAP1 silencing significantly inhibited A549 cell proliferation, increased the percentage of cells in G₀/G₁ phase (P<0.01), and significantly decreased the migration and invasion of A549 cells (P<0.01). Conclusion YAP1 silencing can inhibit malignant biological characteristics of NSCLC, which suggests that YAP1 gene may serve as an important target in the gene therapy of lung cancer.