This study develops selenized potato resistant starch (P‐RS4·Se) from Enshi potato starch to enhance bioactivity. First, the resistant starch (P‐RS4) is prepared through high‐temperature citric acid esterification. Then, P‐RS4 is selenized using the nitrate‐sodium selenite method and analyzed with Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), X‐ray Photoelectron Spectroscopy (XPS), and Nuclear Magnetic Resonance (NMR). Optimal conditions are identified: 0.7 % HNO3, a 1:1.1 ratio of P‐RS4 to Na2SeO3, 65 °C, and 4 h. Selenization disrupts P‐RS4·Se’s microstructure, forming a Se─O─C bond with ─OH on C6. The selenized starch shows strong in vitro antioxidant effects, protecting A549 lung cancer cells from oxidative damage at 6–8 mg mL−1, supporting selenium supplementation.