BACKGROUND: Histone methyltransferase G9a has been primarily understood as a co-repressor of gene expression, but it has been showed G9a also positively regulates nuclear receptor mediated transcription. MCM7, a critical component of the DNA replication licensing complex, is amplified and over-expressed in a variety of human malignancy. The objectives of the present study were to study the relationship between the expression of G9a and MCM7 and the pathological grades, clinical stages and prognosis of esophageal squamous cell carcinoma (ESCC). METHOD: We collected 139 formalin-fixed and paraffin-embedded tissues from patients having ESCC and surveyed them by tissue microarray-based immunohistochemical staining. The association between expressions of MCM7 and G9a, clinicopathological parameters, and prognosis of ESCC was examined. RESULTS: From tissue microarray immunohistochemistry staining results, we found that the nuclear staining intensity of MCM7 and G9a was associated with histologic grade (p=0.000; 0.000), tumor depth (p=0.050; 0.034), lymph node metastasis (p=0.001; 0.009), and tumor stage (p=0.000; 0.003). The expression of G9a was correlated with that of MCM7 in ESCC. G9a over-expression independently predicted poor cancer-specific survival in ESCC (hazard ratio: 0.05, 95% confidence interval: 0.006-0.417, p=0.006), and MCM7 (hazard ratio: 0.05, 95% confidence interval: 0.013-0.441, p=0.004). ESCC patients who had double possitive expressions of both G9a and MCM7 (G9a+MCM+) had much shorter survival than those from either G9a or MCM7 low expression groups (G9a-MCM-, G9a+MCM-, G9a-MCM+). CONCLUSION: MCM7 and G9a may serve as effective prognostic factors and could also be used as biomarkers for predicting various clinical outcomes of ESCCs in the Chinese population. This article is protected by copyright. All rights reserved.