The co-processing of solid and hazardous waste in cement kilns raises the concentration of harmful substances in flue gas, posing challenges to the stable and efficient operation of wet flue gas desulfurization systems. This paper analyzes the main operational problems of wet desulfurization systems during co-processing, including slurry poisoning, intensified equipment corrosion, and decreased desulfurization efficiency. The sources of harmful elements such as chlorine, fluorine, and heavy metals are clarified, and their multi-level enrichment pathways and action mechanisms are expounded from three aspects: the low-temperature area of the raw mill, slurry circulation in the desulfurization tower, and reuse of desulfurization wastewater. Combined with engineering practice, comprehensive optimization and renovation schemes are proposed from three perspectives of equipment anti-corrosion, wastewater zero discharge, and automatic control. The operation results show that the desulfurization efficiency exceeds 98% and full wastewater zero discharge is realized, with a significant reduction in annual operating cost. The research conclusions can provide a technical reference for the design, operation and maintenance of desulfurization systems in similar engineering projects.