P53　mutation　is　the　most　frequent　DNA　mutation　that　occurs　in　almost　all　human　tumors　and　has　been　detected　in　different　areas.　This　tumor　suppressor　gene　maintains　the　integrity　of　the　genome　while　the　mutation　in　the　gene　increases　susceptibility　to　various　cancers.　Human　Papillomavirus　(HPV)　infection　is　a　risk　factor　for　certain　cancers　such　as　cervical　cancer　and　esophageal　cancer　as　well.As　TP53　expression　and　mutation　have　different　results　in　different　areas,　in　this　study　we　analyzed　the　p53　mutation　in　HPV　positive　and　negative　of　113　esophageal　cancer　patients　in　the　Tangshan　area　of　China.　In　this　case,　we　extracted　DNA　from　the　formalin　fixed　paraffin　embedded　(FFPE)　tissue　blocks　of　113　esophageal　cancer　patients.　PCR　for　detection　of　HPV　and　TP53　mutations.　And　then　the　Chi-square　test　was　used　to　analyze　mutations　results.　Our　result　including　59　Squamous　Cell　Carcinoma　(ESCC)　cases　and　54　Adenocarcinomas　(AC).　AC-HPV　positive　patients　had　4(12.9%)　mutations　and　negatives　patients　had　7(30.43%)　mutations　while　ESCC_HPV　positive　patients　had　3(7.69%)　mutations　and　HPV-ESCC　negative　patients　had　7(35%)　mutations,　(P=　0.024).　HPV　negative　showed　more　mutation　frequency　in　compare　with　HPV　positive　in　this　area.　In　conclusion:　this　research　demonstrates　the　reverse　relationship　between　HPV　distribution　and　P53　mutation　frequency.　However,　the　very　low　rate　of　Tp53　mutation　was　detected　and　most　of　them　are　found　in　exon　4.　Which　it　may　be　related　to　the　elevated　percentage　of　high-risk　HPV.　But　more　experiments　also　on　TP53　polymorphisms　are　suggested　to　understand　the　reason　behind　these　low　frequency.