〔Abstract〕 Objective To investigate the expression and clinical significance of CD155 in oral squamous cell carcinoma(OSCC) tissues, as well as its impact on migration, proliferation and invasion. Methods Immunohistochemistry(IHC) was used to analyze the expression of CD155 in OSCC tissues and its correlation with clinicopathological features and prognosis. The transcription levels of CD155 were assessed by Western blot and RT-qPCR. Cell experiments were conducted to evaluate the effects of CD155 on OSCC cells following transfection with CD155 siRNA. Results CD155 was predominantly expressed on the cell membrane in OSCC tissues, with higher expression levels compared to normal tissues(χ2=50.750, P<0.000 1). High CD155 expression was associated with Ⅲ+IV disease stages(χ2=25.488, P=0.001), poor differentiation(χ2=6.299, P=0.012), T3+T4 depth of invasion(χ2=23.820, P=0.001) and lymph node metastasis(χ2=7.830, P=0.005) in OSCC patients; survival analysis revealed a correlation between high CD155 expression and shorter patient survival(P<0.05). COX regression analysis identified lymph node metastasis as an independent factor affecting the survival of OSCC patients(P<0.05). Both CD155 protein expression and mRNA transcription levels were significantly upregulated in OSCC cells(P<0.05). Transfection with siRNA-CD155 in OSCC cells resulted in significantly reduced proliferation, migration and invasion abilities compared to the control group(P<0.05).Conclusion CD155 is highly expressed in OSCC tissues and is associated with poor patient prognosis. Modulating CD155 expression can influence the biological functions of OSCC cells, leading to and inhibition of proliferation, migration, and invasion.