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Our study confirms the important role of TNF-α and sustains that it might be a therapeutic target in OSCC. TNF-α is a key mediator of the immune system, with important role in OSCC tumorigenesis, and might be considered as a therapeutic target using siRNA technology, particularly for those risk cases having FASL/FADD overexpressed. TNF-α is a key mediator of the immune system, with important role in OSCC tumorigenesis, and might be considered as a therapeutic target using siRNA technology, particularly for those risk cases having FASL/FA