FKBP10 knockdown significantly inhibited proliferation, colony formation (35%-40% reduction), migration (30%), and invasion (50%), while markedly enhancing radiosensitivity through increased DNA damage (<i>γ</i>H2AX foci increased twofold, <i>p</i> < 0.01) and strand breaks (comet tail DNA: 22% → 43%, <i>p</i> < 0.01).<h4>Conclusions</h4>This multiomics study establishes FKBP10 as a robust CAF-derived biomarker and functional therapeutic target for radiotherapy resistance in CRC, providing a foundation for developing FKBP10-targeted combination strategies for precision cancer treatment. The gene discussed is H2AX; the disease is colorectal carcinoma.