Hydrogen chloride (HCl) is a typical contaminant generated in waste combustion, whose emission is strictly regulated. In order to cope with severe limits issued by local authorities on the annual mass flow of HCl emitted, several European waste-to-energy plants perform at least a two-stage abatement of the pollutant and operate with a set-point for HCl concentration at stack well below the hourly emission limit imposed by the Industrial Emissions Directive. Even though the operating conditions in a WtE facility are highly variable (both in terms of HCl release from the burnt waste and of operating temperature of the HCl removal system), it is common industrial practice to keep both the set-point for HCl concentration at stack and the set-point for HCl concentration between the two abatement stages at a constant value. However, this might force the abatement system to operate far from its design conditions and from the optimal reactivity window of the adopted HCl removal agent, thus increasing the consumption rate of reactant and the consequent generation rate of process residues. Both the supply chain of reactants and the management of residues generate environmental impacts. The present work demonstrates that the adoption of variable values for both set-points can provide cost savings and indirect environmental benefits, thanks to the reduction of reactant consumption and residue generation. By considering as case study a WtE plant equipped with a two-stage dry HCl removal system, a year of operation of the plant was analysed. The operating costs and life cycle impacts generated by the actual operation of the HCl treatment system with constant set-points were compared with those generated if the plant had operated with variable set-points, simulated with a semi-empirical model for HCl removal tuned on historical process data from the plant. A 13 % reduction of the life cycle global warming impact and an 8 % reduction of the life cycle acidification impact, in addition to 10 % cost savings, were associated to the utilisation of variable set-points.