Animal experiments confirmed that the tumor volume in the PTEN-OE + IR group was significantly lower than that in the NC + IR group, with an expanded necrotic area, a decreased Ki67 index, and an increased TUNEL-positive rate.<h4>Conclusion</h4>PTEN enhances the radiosensitivity of melanoma by inhibiting the DNA-PKcs signal, weakening NHEJ repair, and delaying cell-cycle recovery. The gene discussed is PRKDC; the disease is melanoma.