In brief, we found that inhibition of SHP2 in EGFR T790M mutant LUAD cells can improve the sensitivity of tumor cells to Osimertinib, and the mechanism is that inhibition of SHP2 suppresses the CSCs by blockade of CXCL8-CXCR1/2 positive feedback loop. Here, CXCL8 is linked to neoplasm.