Based on this, we first explored the expression levels of representative pain genes (NAV1, EHMT2, SP1, SLC6A4, COMT, OPRM1, OPRD1, CYP2D6, and CYP3A4) in KIRC, their prognostic significance, their roles in cancer functional states, their DNA methylation and their relevance to tumor immunotherapy (anti‐PD‐1 therapy, anti‐PD‐L1 therapy, and anti‐CTLA4 therapy) and immunomodulator (Iimmunoinhibitor, immunostimulator, and MHC molecule), which added crucial new members to the genomics of KIRC and provided the new references for clinical immune personalized therapy. Here, CYP3A4 is linked to cancer.