Nasopharyngeal　carcinoma　(NPC)　is　an　epithelial　malignancy　facilitated　by　Epstein-Barr　Virus　infection.　Here　we　resolve　the　major　genetic　influences　for　NPC　incidence　using　a　genome-wide　association　study　(GWAS),　independent　cohort　replication,　and　high-resolution　molecular　HLA　class　I　gene　typing　including　4,055　study　participants　from　the　Guangxi　Zhuang　Autonomous　Region　and　Guangdong　province　of　southern　China.　We　detect　and　replicate　strong　association　signals　involving　SNPs,　HLA　alleles,　and　amino　acid　(aa)　variants　across　the　major　histocompatibility　complex-HLA-A,　HLA　-B,　and　HLA　-C　class　I　genes　(PHLA-A-aa-site-62　=　7.4x10(-29);　P　(HLA-B-aa-site-116)　=　6.5x10(-19);　P　(HLA-C-aa-site-156)　=　6.8x10(-8)　respectively).　Over　250　NPC-HLA　associated　variants　within　HLA　were　analyzed　in　concert　to　resolve　separate　and　largely　independent　HLA-A,　-B,　and　-C　gene　influences.　Multivariate　logistical　regression　analysis　collapsed　significant　associations　in　adjacent　genes　spanning　500　kb　(OR2H1,　GABBR1,　HLA-F,　and　HCG9)　as　proxies　for　peptide　binding　motifs　carried　by　HLA-A*11:01.　A　similar　analysis　resolved　an　independent　association　signal　driven　by　HLA-B*13:01,B*38:02,　and　B*55:02　alleles　together.　NPC　resistance　alleles　carrying　the　strongly　associated　amino　acid　variants　implicate　specific　class　I　peptide　recognition　motifs　in　HLA-A　and　-B　peptide　binding　groove　as　conferring　strong　genetic　influence　on　the　development　of　NPC　in　China.