BAG-1 is a multifunctional protein that interacts with a wide range of target molecules to regulate apoptosis. However, the exact mechanism by which BAG-1 inhibits apoptosis is unknown. In the current study, we comprehensively investigate BAG-1 mediated changes in gene expression by comparing the gene expression profile after BAG-1 siRNA silencing in the human lung adenocarcinoma cell line A549. Microarray assay revealed that expression of 589 genes was altered, including 177 upregulated and 412 downregulated genes. Real-time PCR assay of the changes in gene expression indicated a concordance of 86.48% (64/74) with that observed by microarray. The upregulated genes included EGFR, Jun, HSPA1A and CASP7; while the downregulated genes included Lyn, HRAS and TGFalpha. Furthermore, we confirmed by western blot that the expression of EGFR, Jun and HSPA1A were significantly increased, while expression of Lyn and HRAS were dramatically decreased after BAG-1 gene silencing. After transfection with BAG-1 siRNA, lung cancer cell lines A549 and L9981 exhibited significantly enhanced sensitivity to cisplatin-induced apoptosis. Thus, silencing of the BAG-1 gene resulted in changes in expression of apoptosis-related genes and sensitized A549 and L9981 cells to cisplatin-induced apoptosis.