In this study, we identified an enhanced dependency on the mSWI/SNF complexin POU2F3-driven SCLC cells through CRISPR screening and pharmacological validation.Epigenomics analyses revealed that inactivation of the mSWI/SNF complexpreferentially obstructed chromatin accessibility of POU2F3 complexes, leading to adramatic downregulation of POU2F3 signaling. This evidence concerns the gene POU2F3 and small cell lung carcinoma.