IRF3 and neoplasm: Our findings demonstrate that the KMT5C‐mediated DNA damage response inhibits STING‐IRF3 signaling activation, resulting in the suppression of the type I IFN response, particularly CCL5 expression, leading to the downregulation of CD8+ T cell infiltration and function in NSCLC, which is required for the promotion of tumor immune evasion and NSCLC progression.