Background Colon adenocarcinoma (COAD) is one of the common cancers worldwide. Collagen triple helix repeat containing 1 (CTHRC1) has been reported to be involved in cell invasion, angiogenesis, and the promotion of epithelial-mesenchymal transformation by mediating multiple signaling pathways. However, the role of CTHRC1 in COAD has not yet been determined. Methods Differentially expressed genes were evaluated using gene expression data from the Oncomine and TIMER databases. Correlations between CTHRC1 gene expression and clinicopathological factors were analyzed using gene expression data from UALCAN databases. Then, we searched the GEPIA database to evaluate the association of CTHRC1 gene expression with clinical outcomes. The cBioPortal database was used to analyze CTHRC1 genetic alterations. Subsequently, the TIMER website was chosen to assess the correlation of CTHRC1 with the tumor immune cell infiltration level. The TCGA dataset was used for a gene set enrichment analysis (GSEA). Result CTHRC1 was highly expressed in COAD patients, and significantly related to poor prognosis. In addition, elevated expression of CTHRC1 was related to the clinical stage and pathological type of COAD. The GSEA analysis showed that CTHRC1 was enriched in Gα signaling, GCPR ligand binding, neutrophil degranulation, interleukin signaling, and tumor-associated pathways. In addition, CTHRC1 was significantly associated with the expression of multiple immune markers related to specific immune cells. Conclusion This study suggest that CTHRC1 expression is related to the prognosis and immune infiltration of COAD patients. Therefore, CTHRC1 may be a new candidate prognostic biomarker for determining immune infiltration levels and providing COAD prognoses.