X-ray repair cross-complementing protein 1 (XRCC1) could repair cisplatin-induced DNA damage. XRCC1 Arg399Gln and Arg194Trp variants alter XRCC1 expression and function, leading to changes in cancer sensitivity to cisplatin treatment. This study aimed to investigate the effects of XRCC1 Arg399Gln and Arg194Trp polymorphisms on cell viability, apoptosis and XRCC1 expression in cisplatin-sensitive A549 and cisplatin-resistant A549/DDP nonsmall cell lung cancer (NSCLC) cells. Plasmids carrying XRCC1 Arg399Gln and Arg194Trp were constructed and transfected into A549 and A549/DDP cells. RT–PCR, Western blot, MTT assay, and flow cytometry analysis were performed to assess cell viability, apoptosis, and XRCC1 expression. Compared to control cells, the viability of A549 and A549/DDP cells transfected with XRCC1 Arg399Gln and Arg194Trp was higher and the apoptosis rate was lower, and XRCC1 mRNA and protein expression levels were significantly higher. In conclusion, our results suggest that XRCC1 Arg399Gln and Arg194Trp polymorphisms change XRCC1 expression in NSCLC cells and alter the sensitivity of NSCLC to cisplatin-based chemotherapy