Considering that the IFNI is involved in the regulation of immune response against cancer and that TG2 negatively regulates the activation of its main transcription factor IRF3, reducing the IFNβ expression, in this study, we investigated whether TG2 is involved in a specific mechanism of immune evasion of cancer cells, by limiting the stimulation of immune system response acting on the IRF3/STING/TBK1 pathway. The gene discussed is IRF3; the disease is cancer.