Nasopharyngeal carcinoma (NPC) is an Asia-prevalent malignancy, yet its genetic underpinnings remain incompletely understood. Here, a transcriptome-wide association study (TWAS) is conducted on NPC, leveraging gene expression prediction models based on epithelial tissues and genome-wide association study (GWAS) summary statistics from 1577 NPC cases and 6359 controls of southern Chinese descent. The TWAS identifies VAMP8 on chromosome 2p11.2 as a novel susceptibility gene for NPC. Further fine-mapping analyses pinpoint rs1058588, located within VAMP8, as a causal variant through eQTL colocalization, and GWAS analyses across multiple cohorts, achieving GWAS significance (OR = 1.18, P = 3.09 × 10