A frame differencing pixel (FDP) design based on fully depleted silicon-on-insulator (FD-SOI) technology is presented, demonstrating the capability of the FDP to perform pixel-level real-time frame difference (FD) for motion extraction and image preprocessing. The photo charges are collected by the diode under the buried oxide (BOX) and sensed by the MOSFET above. The capacitance of the BOX is used to generate the FD signal without incurring more area costs. TCAD simulations of the FD-SOI FDP were performed to help the analysis. An optimal pixel design model was developed to describe the relationship between noise performance and area allocation. According to the simulation results, the FDP could achieve light sensitivity of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$25.6 ~\mu \text{A}$ </tex-math></inline-formula> /( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\mu \text{J}$ </tex-math></inline-formula> /cm2) and a differential signal-to-noise ratio of 35 dB with a <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$4 ~\mu \text{m}$ </tex-math></inline-formula> pixel pitch and 76% fill factor.