We found that AFAP1-AS1 enhances KAT2B acetyltransferase activation, which upregulates H3K14ac activity against TIF1α, resulting in enhanced RBM3 transcription and subsequent stabilization of YAP mRNA, inducing AFAP1-AS1-driven NPC tumorigenicity. Here, PTGDR is linked to nasopharyngeal carcinoma.