【Abstract】 Objective To study the expression of SCNN1B in non small cell lung cancer (NSCLC) tissues and its regulation for lung cancer sensitivity to cisplatin. Methods The pathological specimens of 130 NSCLC patients who were diagnosed and treated in the hospital from December 2017 to December 2019 were enrolled as the research objects. The level of SCNN1B mRNA in lung cancer tissues of NSCLC patients was detected by RT-PCR. A549 and A549/DDP cell lines were collected, and A549 cell group, A549/DDP cell group, siRNA-SCNN1B group and siRNA-NC group were set up. The siRNA-SCNN1B group and siRNA-NC group were transfected with plasmid of SCNN1B overexpression and empty plasmid (negative control). The relative expression levels of various SCNN1B mRNA were detected by RT-PCR to verify the transfection effect of SCNN1B. The half inhibitory concentration (IC50), apoptosis and cell cycle in each group were detected. The expression of resistance related proteins was detected by Western blot. Results The low expression rate of SCNN1B mRNA in patients with poorly differentiated NSCLC was significantly higher than that with moderately and highly differentiated NSCLC. The low expression rate of SCNN1B mRNA in patients with TNM staging at stage IV was significantly higher than that at stage III (P＜0.05). The level of SCNN1B mRNA in A549/DDP cell group were significantly lower than that in A549 cell group (P＜0.05). Compared with A549/DDP cell group, level of SCNN1B mRNA in siRNA-SCNN1B group was significantly increased (P＜0.05). IC50 in siRNA-SCNN1B group was significantly lower than that in siRNA-NC group, and the reversal coefficient was decreased by (221-69±26-27)% (P＜0.05). Compared with A549 cell group, apoptosis rate in A549/DDP cell group was significantly decreased, while proportion of cells at G0/G1 phase was significantly increased (P＜0.05). Compared with the A549/DDP cell group, apoptosis rate in siRNA-SCNN1B group was significantly increased, while proportion of cells at G0/G1 phase was significantly decreased (P＜0.05). Compared with A549 cell group, Bcl-2, survivin, cyclin D1 (CyclinD1), epidermal growth factor receptor (EGFR), multidrug resistance related protein-1 (MRP1) and lung resistance related protein (LRP) levels were significantly increased in A549/DDP cell group (P＜0.05). Compared with A549/DDP cell group, Bcl-2, survivin, CyclinD1, EGFR, MRP1 and LRP levels were significantly decreased in siRNA-SCNN1B group (P＜0.05). 〖WTHZ〗Conclusion〖WTBZ〗 SCNN1B is closely related to differentiation degree of lung cancer tissue and tumor staging in NSCLC patients. Targeting upregulation of SCNN1B can down regulate the protein expressions of Bcl-2, survivin, Cyclin D1, EGFR, MPR1, LRP.