This paper reports on a study that contributed to the process design of an industrial-scale energy-from-waste (EfW) combustion plant that processes over 250 000 tonnes of waste and produces 34 MWe of electric energy. The study also investigates the effect of replacing the conventional calcium hydroxide sorbent with sodium bicarbonate in the removal of acidic pollutants from the flue gas. Hydrated lime is widely used to remove acidic pollutants such as HCl, SO2, and HF from flue gas streams in municipal solid waste (MSW) combustion. However, it is corrosive, it is required in excess, and it requires low operating temperatures for the removal to be effective. Mass and energy balances of the process were performed using the proximate and ultimate analyses of the waste and a mathematical model based on the unreacted-core model has been applied to compare the efficiency of using both sorbents. The economic feasibility of using sodium bicarbonate instead of hydrated lime in the plant has also been investigated. This study showed that although sodium bicarbonate is a more expensive sorbent, it is more efficient, and it is economically a more attractive option for the removal of acidic pollutants than hydrated lime.