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Objective:To investigate the mRNA and protein expression of histone methyltransferase G9a and its clinical significance in extrahepatic cholangiocarcinoma. Methods: Using RT-PCR and Western Blotting to detect the expression of G9a at the level of mRNA and protein in 48 tumor samples and 39 control tissues. Results: The mRNA and protein expression of G9a in extrahepatic cholangiocarcinoma was higher than control statistically (P ＜ 0.05) and positively correlated with lymph metastasis (P ＜ 0.05) and TNM stage (P ＜ 0.01). Conclusion: The significant difference of G9a expression between tumors and control implicated that the important role of histone methylation disruption resulted from increased G9a expression in extrahepatic cholangiocarcinoma.