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Impact of temperature and process variations on the output voltage variations of CMOS photo sensor is discussed. As temperature becomes high, output voltage (Vout) decreases because of the amplifier characteristics. But above 350 K, Vout increases in a weak light intensity range. The process variations have an impact when the operation temperature is high and irradiating light intensity is low. We also estimate influence of additional drive-in process, and find the sensitivities of process variation to increase. To consider both process and temperature variations at the same time, we evaluate Vout variation with mixed-mode simulation.