Abstract: Objective：To investigate the expression of MUC15 in esophageal squamous cell carcinoma (ESCC) and its relationship with the occurrence and development of ESCC. Methods：The mRNA levels and protein expression rates of MUC15 in 53 cases of normal esophageal mucosa tissue, 20 mucosa tissue adjacent to cancer and 53 ESCC tissue samples were determined by RT-PCR and the SP immunohistochemical method, respectively, and the expression difference of MUC15 between different tissues was compared. Results：The relative mRNA levels of MUC15 gene in the normal esophageal mucosa tissue, mucosa adjacent to cancer and ESCC tissue were 0.281±0.017, 0.322±0.029 and 0.790±0.038, respectively, and the protein expression rates 20.7%, 35.0% and 88.7%, respectively, with significant difference between different tissues (P<0.05). In addition, the relative mRNA levels and protein expression rates of MUC15 in stages 0～Ⅱ and Ⅲ～Ⅳ of ESCC were 0.498±0.029, 0.832±0.045 and 70.0%, 93.0%, respectively, with significant difference between them (P<0.05). Moreover, there was also significant difference of relative mRNA levels (0.829±0.031 vs 0.501±0.042) and protein expression rates (90.2% vs 75.0%) of MUC15 between ESCC with and without lymph node metastasis (P<0.05). Conclusion：The expression levels of MUC15 gene and protein in ESCC tissue are significantly higher than that in normal esophageal tissue, indicating that they may be associated with the carcinogenesis and development of ESCC.