The two-stage chemical absorption-biological reduction (CABR) system, comprised of an absorption column and a bioreactor, is regarded as a promising option for NO removal from the middle-and small-sized boilers. In this work, a steadystate rate-based model was developed for the two-stage CABR system. The developed model was validated by the data obtained from a laboratory two-stage CABR setup and then used for the estimation of the footprints for treating a 5 × 10 4 m 3 h −1 flue gas from a 14 MW coal-fired steam boiler. For a baseline case (L/G = 10 L m −3 , C in,NO = 350 ppm, C in,O 2 = 6% (v/v)), the designed absorption column size was 3.60 × 8.75 m (d × h), while the bioreduction column was set at 3.60 × 8.50 m (d × h). Furthermore, sensitive analysis including the influence of gas concentrations, packing properties, and microorganism activities was investigated to optimize the design and operation of two-stage CABR process. Under optimized conditions, the footprint of the bioreactor can be downsized by 22.74%. It is believed that this work can provide fundamental data for the industrial application of the two-stage CABR system in the middle-and small-sized boilers.