Background Transmembrane 4 L six family member 5 (TM4SF5) has been found to play a vital role in the cancer process, but the relationship between TM4SF5 and colorectal cancer remains unclear. Therefore, the present study aimed to investigate the clinical and prognostic value of TM4SF5 in colorectal cancer (CRC). Methods Immunohistochemistry and RT-qPCR were used to identify the clinical significance and prognostic value of TM4SF5 expression in colon cancer. The expression of TM4SF5 was knocked down using the siRNA method to evaluate the role of TM4SF5 in regulating the biological behavior of colon cancer cell lines. Results The immunohistochemistry study revealed that the expression of TM4SF5 in human colorectal cancer tissues was significantly higher than that in adjacent normal tissues (P < 0.0001). However, there was no correlation between the expression of TM4SF5 and the clinicopathological features of these patients. The RT-qPCR analysis revealed that the mRNA expression of TM4SF5 was higherin colon cancer cell lines than in normal cells (P < 0.05). The survival analysis revealed that the overall survival (OS) rate of patients with a low expression of TM4SF5 was significantly higher, when compared to patients with a high expression of TM4SF5 (P = 0.048). The COX model revealed that the expression of TM4SF5 (P < 0.001) and clinical stage (P = 0.025) can be used as independent prognostic factors for patients with colon cancer. In addition, the knockdown of TM4SF5 in colon cancer cell lines LoVo, SW480, RKO and HCT-116 significantly reduced the ability of cells (such as proliferation, migration and invasion). Conclusion The present results indicate that the increase in TM4SF5 expression in human colon cancer is associated with cancer progression and poor survival, and that its intervention can be an important therapeutic strategy against colon cancer.

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