Background: Colon cancer is one of the most lethal cancers in the world. NDC1 is a crucial membrane-integral nucleoporin of nuclear pore complexes. The clinical significance of NDC1 in colon cancer has not been demonstrated to date. Therefore, we determined to evaluate the association between NDC1 and colon cancer using the open-access database. Methods: The TCGA data of colon cancer were extracted to determine the relationship between NDC1 and the clinical characterization. We assessed the predictive role of NDC1 expression in the survival of patients with colon cancer. Univariate and multivariate Cox proportional hazard models were applied to analyze the association between the clinical factors and prognosis. The TIMER database was used to describe the association between immune cell infiltration and specific gene expression in the colon cancer context. Gene set enrichment analysis (GSEA) was performed based on the TCGA dataset. Results: A total of 445 colon cancer patients with complete clinical information were included. NDC1 expression was significantly up-regulated in colon cancer tissues compared to adjacent normal tissues. Univariate and multivariate Cox regression analyses showed that NDC1 was an independent prognostic factor. Patients with a higher level of NDC1 expression tend to survive longer compared to those with a lower level of NDC1 expression. The level of the NDC1 expression is significantly associated with TNM stages. Furthermore, we constructed a nomogram to predict the prognosis by using NDC1 as a factor. The expression of NDC1 was significantly associated with infiltration of B cell, CD8+T cells, macrophages, neutrophils, and dendritic cells in colon cancer lesions. Additionally, NDC1 was predominantly enriched in KRAS-related signaling pathways by GSEA. Conclusion: NDC1 can serve as a prognostic biomarker, which is negatively correlated with aggressiveness and positively associated with immune infiltrates of colon cancer.