Taken together, our findings suggest that the CypA/CD147 axis is a potent therapeutic target for EGFR-mutant NSCLC CSCs and that the natural CypA inhibitors C9 and CsA may serve as novel therapeutic agents to eliminate EGFR-mutant NSCLC CSCs, either as monotherapy or in combination with afatinib. This evidence concerns the gene BSG and non-small cell lung carcinoma.