Therefore, this study aimed to (i) predict the mRNA expression of CD27 in HNSCC tissues using non-invasive, CT-based radiomics technology; (ii) evaluate the correlation between the constructed radiomics model and the related genes and prognosis; and (iii) explore the potential molecular mechanism underlying the expression of CD27 and its relationship with the immune microenvironment. The gene discussed is CD27; the disease is head and neck squamous cell carcinoma.