X-ray silicon-on-insulator (SOI) pixel sensors, “XRPIX,” are being developed for the next-generation x-ray astronomical satellite, “FORCE.” The XRPIX is fabricated with the SOI technology, which makes it possible to integrate a high-resistivity Si sensor and a low-resistivity Si complementary metal oxide semiconductor (CMOS) circuit. The CMOS circuit in each pixel is equipped with a trigger function, allowing us to read out outputs only from the pixels with x-ray signals at the timing of x-ray detection. This function thus realizes high throughput and high time resolution, which enables to employ anti-coincidence technique for background rejection. A new series of XRPIX named XRPIX6E developed with a pinned depleted diode (PDD) structure improves spectral performance by suppressing the interference between the sensor and circuit layers. When semiconductor x-ray sensors are used in space, their spectral performance is generally degraded owing to the radiation damage caused by high-energy protons. Therefore, before using an XRPIX in space, it is necessary to evaluate the extent of degradation of its spectral performance by radiation damage. Thus, we performed a proton irradiation experiment for XRPIX6E for the first time at Heavy Ion Medical Accelerator in Chiba in the National Institute of Radiological Sciences. We irradiated XRPIX6E with high-energy protons with a total dose of up to 40 krad, equivalent to 400 years of irradiation in orbit. The 40-krad irradiation degraded the energy resolution of XRPIX6E by 25  ±  3  %  , yielding an energy resolution of 260.1  ±  5.6  eV at the full-width half maximum for 5.9 keV X-rays. However, the value satisfies the requirement for FORCE, 300 eV at 6 keV, even after the irradiation. It was also found that the PDD XRPIX has enhanced radiation hardness compared to previous XRPIX devices. In addition, we investigated the degradation of the energy resolution; it was shown that the degradation would be due to increasing energy-independent components, e.g., readout noise.