Mechanistically, this work demonstrates that KMT5C activated the DNA repair response to inhibit the STING‐IRF3 pathway, downstream type I IFN signaling, and CCL5 secretion, leading to the downregulation of CD8+ T cell infiltration and function in NSCLC, ultimately facilitating tumor immune evasion and tumor progression. Here, IRF3 is linked to non-small cell lung carcinoma.