BACKGROUND: Colorectal cancer (CRC) is a common tumor of the digestive system. In recent years, CRC has had the fourth highest incidence and second highest mortality rate among tumors worldwide. Therefore, it is important to identify new molecular markers, and examine their relationship with the clinicopathological features and prognosis of CRC patients. This study examined the correlation between the expression levels of the tropomyosin receptor kinase C (TRKC) and neurotrophic factor-3 (NT-3) proteins, and the clinicopathological features and prognosis of CRC patients. METHODS: In total, 141 paraffin-embedded specimens from patients who had undergone radical surgical resection for CRC were analyzed. All CRC diagnoses were confirmed by pathological examination. Corresponding adjacent normal tissues served as controls. Immunohistochemical staining was employed to assess the expression of the TRKC and NT-3 proteins in both the CRC and adjacent normal tissues. A subsequent statistical analysis was conducted to explore the associations between the expression levels of these proteins, and the clinicopathological features and prognostic outcomes of CRC patients. RESULTS: The expression level of CONCLUSIONS: We found that the TRKC and NT-3 proteins were closely associated with the occurrence, metastasis, invasion, and tumor marker levels of CRC, and can be used as independent predictors of prognosis in patients with CRC.