Using genotype data from 1368 HNSCC patients, we found that a germline SNP in MAPK1 (rs8136867, p value = 8.92 × 10−4; OR = 1.33, 95 % CI: 1.13–1.58) showed the highest association with cancer pain. This evidence concerns the gene MAPK1 and head and neck squamous cell carcinoma.