In conclusion, through a targeted MHC sequencing to cancer research and a population‐based replication study as well as functional and molecular investigations, we have identified a novel SNP rs117565607 of TRIM26 gene and the A allele associated with NPC risk that functions to decrease TRIM26 expression through YY1‐mediated transcription and the establishment of a new functional link between TRIM26 downregulation and low immune response in NPC. Here, YY1 is linked to cancer.