Growing evidence indicates that tumor suppressor gene TP-53 and non-coding RNA miR-34b/c independently and/or jointly play crucial roles in carcinogenesis. We hypothesized that the polymorphisms of rs4938723 in the promoter region of pri-miR-34b/c and TP-53 Arg72-Pro may be related to the risk of nasopharyngeal carcinoma (NPC). We performed a case-control study between 217 patients with NPC and 360 healthy controls in a Chinese population using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. A significantly increased risk of NPC was observed in the miR-34b/c rs4938723 CT/CC genotypes compared with the TT genotype (adjusted OR=1.44, 95 % CI 1.02-2.03, p=0.04), and also the C allele (adjusted OR=1.33, 95 % CI 1.04-1.70, p=0.03). The gene-gene interaction of miR-34b/c rs4938723 and TP-53 Arg72-Pro showed that the combined genotypes of rs4938723CT/CC and TP-53CG/CC increased the risk of NPC (rs4938723CT/CC + TP-53CG/CC vs. rs4938723 TT+TP-53 CG/CC: OR=1.58, 95 % CI 1.04-2.42, p=0.03). These findings suggest that miR-34b/c rs4938723 and TP-53 Arg72Pro polymorphisms may singly or collaboratively contribute to the risk of NPC.