Abstract: Objective To investigate the relat ionship betw een p53 mutations and human papillomavirus 16(H PV16)infections in esophageal cancer.Methods p53 mutations and infections were examined by polymerase chain reaction(PCR)and single strand conformation polymorphism(SSCP)and DN A direct sequencing analysis in the 110 exophageal cancers.The case-case study was used for factor anlysis.Results The rate of mutations in exon5-6,exon7,exon8-9 were 19.1%,27.3% and 17.2% respectively.The rate of p53 gene mutation was 61.4% in smoke groups and 48.2% in nosmoker groups.There was a significant difference between them.The rate of p53 gene mutation was 65.2% in lymph node metastasis groups and 37.5% in nolymph no de metastasis groups.There was significant difference between them.The rate of p53 gene mutation was 40.7% in HP V16 negative groups and 57.1% in HPV 16 positive groups,There was no association between HPV 16 status and p53 mutations.Conclusion High-risk HPV plays an important role in the development of esophageal cancer.There is a significant difference between p53 mutations and lymph node metastasis.This result may predict that the cases could be deter iorated after the operation.p53 gene mutations may play an important role in the mechanism of esophageal cancer and support the relationship between p53 mutatio ns and HPV infection not to be mutually exclusive.