To identify the common downstream targets of the PTTG3P/ILF3 complex and the mechanisms driving the malignant progression of NSCLC, we used RNA transcriptome sequencing, bioinformatics analysis, and qRT-PCR validation to find that MAP2K6 and E2F1 expression levels were evidently downregulated in PTTG3P-knockdown NSCLC cells; simultaneously, qRT-PCR assay also found that the expression levels of MAP2K6 and E2F1 mRNAs were significantly downregulated in ILF3-knockdown NSCLC cells. The gene discussed is E2F1; the disease is non-small cell lung carcinoma.