The structural features and the energy deposition process of γ-ray photons in the pixels for the 4 transistors pinned photodiode active pixel sensors (4T-PPD-APSs) are analyzed. By the establishment of simulation calculation models of sensor pixels and pixel array and by the experiment of γ-ray radiation response, the response characteristics of the active pixel sensors (APS) under different photon energies and different radioactivity level conditions are investigated. The research results show that, the energy deposition of the γ photon at the photodiode spatial charge area and the formation of diffused photocurrent are the root causes for the photon response phenomena occurring in the APS. The mean pixel value first increases and then tends to saturate with the increase of the dose rate. When the multiple peaks appear in the typical event areas, the statistical pixel value cannot accurately reflect the radioactivity level of the radiation fields.