In this paper, a 500×500 digital pixel sensor (DPS) based on pulse frequency modulation (PFM) is proposed with dynamically biased multiple integration.By sequentially compressing the photo-response curve and dynamically adjusting the bias current, the dynamically biased multiple integration simultaneously improves the dynamic range and the power efficiency of the proposed DPS.To minimize the non-uniformity of the proposed DPS, a modified charge reset circuit is also employed.The proposed DPS is implemented in a 110-nm CMOS process.Post-layout simulation results show that the deviation of photo-response sensitivity and the overall non-uniformity of the proposed DPS are less than ±2% and 1.5%, respectively.The proposed DPS achieves a dynamic range of 120.5 dB with a frame rate of 250 fps and a pixel pitch of 21 µm.Each pixel of the proposed DPS consumes 186-301 nW while the whole chip consumes 107 mW, resulting in competitive figure of merits of 1.71 nJ/frame • pix and 1.43 e -• pJ/DRU compared with previous DPSs.