Objective To investigate the effects of tumor necrosis factor-α ( TNF-α ) on the resensitization of human lung cancer cell lines A549/DDP to cisplatin (DDP) and to explore the relationship between the expression of TNF-αand resistance-related protein (LRP) in lung tissue.Methods The cytotoxic effects of combinational treatment by TNF-α and cisplatin on A549/DDP were measured by MTT assay.The expression of LRP was assessed by immunocytochemistry methods.Results The IC50 of A549/DDP to cisplatin were decreased from 7.12 ng/L to 5.02 ng/L,4.41 ng/L respectively by 250 U/ml and 1000 U/ml TNF-α treatment ( P ＜ 0.01 ),with the sensitivity of A549/DDP to cisplatin increased by 1.42 and 1.62 fold respectively.LRP was overexpressed in A549/DDP cell.250 U/ml or 1000 U/ml TNF-α plus cisplatin treatment down-regulated the expression of LRP with the positive rates of ( 60.14 ± 6.54 ) ％ and ( 57.23 ± 5.98 ) ％respectively,which were significantly lower than that of cisplatin alone treatment ( 75.97 ± 5.32 ) ％ and control group (79.63 ± 4.78 ) ％ ( both P ＜ 0.01 ).Conclusion Tumor necrosis factor-α can reverse the resistance of A549/DDP to cisplatin,which may be partially attributed to down-regulating LRP expression.