BACKGROUND: CD155 is a crucial factor in the regulation of T cell function and contributes to immune escape. CD155 upregulation has been found in several types of cancer. However, the mechanism by which CD155 regulates CD8 METHODS: We studied the expression of CD155 in colorectal cancer tissues through western blot, immunohistochemistry, and the TCGA database. We verified the effects of CD155 on the functions of colorectal cancer cells and CD8 RESULTS: We demonstrated that stable CD155 expression was negatively correlated with prognosis in colorectal cancer patients. In vitro experiments confirmed that CD155 does not affect tumor cell proliferation, migration, or invasion. We also revealed that CD155 downregulated the function and migration of CD8 CONCLUSION: This study revealed that CD155 can promote the progression of colorectal cancer by regulating the PI3K / AKT-NF-κB pathway to promote the depletion of CD8