Abstract: Objective This study was designed to explore the prognosis of SWItch/Sucrose Non-Fermentable complex （SWI/SNF） complex subunits mutation and the relation with tumor programmed death ligand 1 （PD-L1） and tumor mutation burden （TMB） in unresectable locally advanced or metastatic non-small cell lung cancer. Methods Patients diagnosed with unresectable locally advanced or metastatic non-small cell lung cancer from April 2019 to September 2020 in the Guangdong Provincial People's Hospital were retrospectively collected. Next-generation sequencing （NGS） was used to detect ARID1A, ARID1B, SMARCA4, PBRM1, ARID2, SMARCB1, and SMARCE1 genomic alterations, TMB was calculated simultaneously, the expression of PD-L1 was detected through immunohistochemistry, and clinicopathological characteristics and survival analysis were carried out in combination with the clinical data of the patients. Results 15.2% （10/66） of patients were found to have two subunits mutation simultaneously; 12 patients （18.2%） were detected with SWI/SNF complex subunit mutations accompanied by KRAS mutation. ARID1A, ARID1B, SMARCA4, PBRM1, ARID2, SMARCB1, and SMARCE1 subunit mutation accounted for 24%, 12%, 34%, 12%, 16%, 1%, and 1%, respectively. 83.7% of patients with SWI/SNF complex subunit mutation expressed PD-L1 ≥ 1%, and the expression of PD-L1≥1% accounted for 22.4% with ARID1A and SMARCA4 mutation, respectively; There was a significant difference in tumor mutation burden （TMB） between SWI/SNF complex subunits （P=0.01）, among which mutation of SMARCA4 accounted for 24.2% when TMB≥ 10 Muts/Mb. Survival analysis showed no significant difference in overall survival among different subunit mutations of the SWI/SNF complex （P=0.61）. Conclusions There was no significant prognostic of survival between different mutational SWI/SNF subunits in unresectable locally advanced or metastatic NSCLC. But patients with SMARCA4 mutation tended to be higher TMB than others, which needs further investigation for its potential clinical value for immune therapy.