Experiments in vitro and in vivo demonstrated that ZNF300 might suppress proliferation and differentiation via inhibiting MAPK/ERK signalling pathway and regulate slow‐cycling phenotype by activating CDK1 through inhibiting WEE1 and MYT1 and modulating MYC/AURKA/BORA/PLK1 axis to promote the chemoresistance and malignant progression of NSCLC. Here, CDK1 is linked to non-small cell lung carcinoma.