Single-event effects (SEEs) induced by medium-energy protons in a 28 nm system-on-chip (SoC) were investigated at the China Institute of Atomic Energy. An on-chip memory block was irradiated with 90 MeV and 70 MeV protons, respectively. Single-bit upset and multi-cell upset events were observed, and an uppermost number of nine upset cells were discovered in the 90 MeV proton irradiation test. The results indicate that the SEE sensitivities of the 28 nm SoC to the 90 MeV and 70 MeV protons were similar. Cosmic Ray Effects on Micro-Electronics Monte Carlo simulations were analyzed, and it demonstrates that protons can induce effects in a 28 nm SoC if their energies are greater than 1.4 MeV and that the lowest corresponding linear energy transfer was 0.142 MeV cm2 mg−1. The similarities and discrepancies of the SEEs induced by the 90 MeV and 70 MeV protons were analyzed.