Lung cancer is a most common malignancy in both men and women. Studies have indicated that YAP gene was closely related to chemo-resistance of cancers. However, whether YAPS expression participates in the resistance of human lung cancer A549 cells to Taxol (TAX) remains unclear. The aim of this study is to investigate the role of YAP in the resistance of A549 cells to TAX. The sensitivity of cells to TAX was firstly confirmed by MTT assay. The expression levels of YAP in A549 cells and A549/TAX cells were examined by QRT-PCR and Western blot. Small interference RNAs (siRNAs) were used to knock down the gene expression of YAP in A549/TAX cells. Then the cell viability and apoptosis were assessed following treatment with taxol using MTT assay and flow cytometry. The levels of drug resistance related genes, MDR1, MRP1 and BCRP, were examined in YAP-siRNA A549/TAX cells. Furthermore, Western blot analysis was utilized to determine ERK pathway following YAP knockdown. The results demonstrated that the expression of YAP was significantly increased in A549/TAX cells. YAP gene knockdown significantly decreased the IC50 value of A549/TAX cells to TAX and increased taxolinduced apoptosis in the A549/TAX cells. The expression of MDR1, MRP1 and BCRP significantly decreased, and YAP knockdown markedly decreased the activation of ERK pathway. In conclusion, YAP knockdown could reverse the resistance of A549/TAX cells to taxol, thus it may act as a candidate for therapeutic target of lung cancer.