In the present study, mRNA sequencing of heterozygous p53-R280T KO CNE2 and control cells showed that heterozygous p53-R280T mutation activated PI3K-Akt signaling pathway, and transfection of wt p53 and p53-R280T mutation plasmid at 1:1 ratio dramatically increased p-AKT levels in the NPC cells with endogenous p53 KO, which was abolished by LY294002. This evidence concerns the gene TP53 and nasopharyngeal carcinoma.