The application of flatbed color scanners for the measurement of color in various industries, especially textile industry, has received a great deal of attention. The initial setup of a scanner and the investigation of factors with a significant effect on scanner outputs are necessary to measure a reliable color using the scanner. In the present study, the setup of a flatbed color scanner was optimized using a full factorial design technique. Three factors, including the scanning position on the glass surface of the scanner (A), cutting size of an image in pixels (B), and bit depth (C), at different levels as input factors, and signal-to-noise ratio and variance of the scanned image as the responses were considered for the evaluation of the reliability of the scanner color measurement. The results of analyzing the factorial design indicate that each of the three factors played a significant role in the scanner setup for the color measurement so that factor A demonstrated the most significant impact on the responses.