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Background Cutaneous squamous cell carcinoma (CSCC) is the second largest nonmelanoma skin cancer in humans; effective treatment options for metastatic CSCC are still in short. In this study, we aimed to explore the function of T‐box transcription factor 2 (TBX2) in CSCC. Methods The expression level of TBX2 was determined in CSCC samples and cell lines. Programmed death ligand 1 (PD‐L1) expression was also analyzed in human CSCC samples. Furthermore, SCC13 cells were transfected with TBX2‐DN (loss of function) or normal TBX2 to check its role in regulating PD‐L1. Results The expression level of TBX2 was positively correlated with the stage of CSCC. CSCC tumor cell lines have significantly higher expression levels of TBX2 than normal skin cell lines, and SCC13 cells showed the highest expression. PD‐L1 expressions were upregulated during the progression of CSCC, and positively correlated with TBX2. Furthermore, PD‐L1 expression increased in SCC13 cells overexpressing TBX2. However, TBX2 did not regulate the activation of IFNγ signal, but mediated the expression of interferon regulatory factor 1 (IRF1) and PD‐L1 in both SCC13 and PDV cells. Conclusion TBX2 could mediate antitumor immune response in CSCC by regulating the expression of PD‐L1 through IRF1. It might be a prognostic marker in CSCC and synergistic target for PD‐1 immunotherapy.