Abstract: Objective To investigate the relationship between the expression of chemotherapy-related genes and epidermal growth factor receptor (EGFR) mutation status, and their impact on chemotherapy response. Methods The IC50 of paclitaxel and cisplatin against A549 and HCC827 cells were measured by MTT assay. The cytotoxicities of paclitaxel, cisplatin and their combination against A549 and HCC827 cells were measured and compared. The expression of chemotherapy-related genes, BRCA1, ERCC1 and TUBB3, were detected by fluorescent quantitative PCR before and after paclitaxel and cisplatin treatment. Results The IC50 of paclitaxel against A549 and HCC827 cells were 100 and 70μg/ml respectively while those of cisplatin were 40 and 50μg/ml, respectively. The cytotoxicity of paclitaxel was stronger against HCC827 cells than A549 cells (P<0.05), while the cytotoxicity of cisplatin was higher against A549 cells than HCC827 cells (P<0.05). The cytotoxicities of the combination were not significantly different against A549 and HCC827 cells (P>0.05) and their combination action showed additive effect (Q=1.03, 1.08). BRCA1 expression in HCC827 cells was significantly higher than that in A549 cells (P<0.05). ERCC1 was up-expressed after treated with cisplatin (P<0.05). Conclusion The killing effect of paclitaxel and cisplatin on EGFR-wild and mutant lung adenocarcinoma cells are significantly different, while the combination are not, which may be related with the expression of BRCA1. EGFR-wild lung adenocarcinoma cells are much easier to appear cisplatin-resistance than mutant phenotype.