In the current study, our results demonstrated echinomycin effectively induced the degradation of MYC and HIF1α and inhibited the growth of p53 deficient lung cancer cells, which suggests the function of echinomycin on MYC and HIF1α is p53-independent and it can be used for the treatment of both p53 wild-type and mutated cancers. This evidence concerns the gene TP53 and lung cancer.