Objective：To explore the relationship between nuclear pore membrane protein 121（POM121）expression and pathological characteristics of patients with colon cancer and the significance of POM121 to patients’ prognosis. Methods：Immunohistochemistry was used to detected POM121 level in colon cancer tissues and para-carcinoma tissues. Based on the clinical data of patients，the connection between POM121 expression and clinical pathological characteristics of colon cancer was analyzed，as well as the significance of POM121 to clinical prognosis. Results：The positive expression rate of POM121 in colon cancer tissues（66.03%）was higher than that in para-carcinoma tissues（47.42%）with a statistically significant difference（P < 0.001）. The expression of POM121 was significantly correlated with tumor siae（P=0.041），lymph node metastasis（P < 0.001），distant metastasis（P=0.002），the AJCC staging（P=0.003），venous invasion（P < 0.001），perineural invasion（P < 0.001），preoperative carcino-embryonic antigen（P < 0.001），preoperative carbohydrate antigen 199（P=0.004），and Ki67（P < 0.001）expression，while no correlation was found between the POM121 expression and gender，age，location，histological type，or differentiation. Patients with high POM121 expression had poor overall survival rates. Genes in colon cancer tissues with high POM121 expression were enriched in aminoacyl t-RNA biosynthesis，base excision repair，DNA replication and so on. Conclusion：POM121 is highly expressed in colon cancer and is an independent risk factor affecting the prognosis of patients. POM121 has the potential to become a new prognostic markers and molecular targets for targeted therapy of colon cancer