Objectives: To explore the expression of manganese superoxide dismutase (MnSOD) in esophageal squamous cell carcinoma (ESCC) and its relationship with clinicopathological characteristics and biological behavior. Methods: On 45 patients with ESCC, immunohistochemistry (SP method), reverse transcription-polymerase chain reaction (RT-PCR), and Western blot were used to detect MnSOD protein and mRNA expression in ESCC and in its adjacent normal tissue 5 cm apart from the edge of cancer lesion and without documented microscopic invasive cancer. Meanwhile, the relationship between the pathological features of esophageal cancer and its biological behavior was analyzed. Results: In ESCC and normal esophageal tissue, MnSOD protein expression was identified 31.1% (14/45) and 86.7% (31/45) (P = 0.000), respectively, with the relative expression levels of MnSOD mRNA 0.310 +/- 0.036 and 0.482 +/- 0.053 (P = 0.000), relatively. Western blot study showed that the relative expressions of MnSOD protein in cancer lesion and in adjacent normal tissue were 0.384 +/- 0.038 and 0.766 +/- 0.041, respectively (P = 0.000). With longer lesion, deeper invasion, and poorer differentiation, the expression of MnSOD would get lower, indicating that the levels of MnSOD protein and mRNA expression were closely related to the length of lesion, depth of invasion, and degree of differentiation in ESCC (P < 0.05). Nevertheless, the result showed no association with the presence of lymph node metastasis, cancer location, and macroscopic classification (P > 0.05). Conclusions: MnSOD protein and mRNA expression both decreased in ESCC, which may be related to carcinogenesis and the development of esophageal cancer. Therefore, detecting the expression of MnSOD in esophageal carcinoma would be of clinical significance in understanding its biological behavior and in guiding therapeutic strategy of esophageal cancer.