Abstract: Objective : To investigate the correlation of Helicobacter pylori L type (Hp-L) and mitochondrial DNA microsatellite instability (mtMSI) with esophageal squamous cell carcinoma (ESCC). Methods : Using Giemsa staining, immunohistochemistry (IHC) staining and polymerase chain reaction (PCR), we detected Hp-L infection rate in 46 samples of ESCC and corresponding normal tissues at the incision margin. PCR technique was used to amplify the urase gene fragment of Hp . Hp-L morphological characters were observed by Giemsa staining and light microscope. The mitochondrial DNA(mtDNA) was amplified by Genepha Long PCR Kit. PCR product was regarded as the template. (C)n and (CA)n locus that existed in the D-loop zone of template mtDNAwere amplified. The PCR product MSI was analyzed by PCR-SSCP technique. Results : The Hp infection rate was 65.2% (30/46) in ESCC, higher than that in normal control tissues. The main shape of Hp was Hp-L type which distributed into or beside nests of carcinoma. Acorrelation was found between Hp-L infection and ESCC. The invasive depth of tumor tissues and the regional lymph node metastasis were correlated with Hp-L infection. mtMSI detection rate was 32.6% (15/46) in 46 case of ESCC, of which 13 cases were examined at (C)n locus of D-loop zone, 5 cases were examined at (CA)n locus, and 3 cases were examined both at (C)n and (CA)n. mtMSI was not found in nomal tissues at the incision margin. No significant relationship was found between mtMSI and clinicopathologic charecteristics. The mtMSI incidence in the 30 cases of ESCC with Hp-L infection was 46.7% (14/30). However, the mtMSI incidence in the 16 cases of ESCC without Hp-L infection was 6.25% (1/16). The difference in the mtMSI detection rate was significant between ESCC with Hp-L infection and ESCC without Hp-L infection. Conclusion : MSI of mitochondrial D-loop zone (C)n locus may play an important role in the carcinogenesis and development of ESCC, and is correlated with Hp-L infection.