Pollution Spill Response Management Model (PSRMM) is required to enhance the decision making process on reservoir operation during accident pollution spill events. To provide an advanced modeling approach, spatial system analyzing (SSA) model, a 2D hydrodynamic and water quality simulation model (CE-QUAL-W2) coupled with Particle Swarm Optimization (PSO) technique address the PSRMM components. The water quality simulation model provides the ability to model the time-of-travel and concentration of pollutant substances at the reservoir, temporally and spatially using real-time stream flow data, outflow data, and the meteorological condition. The coupled simulation-optimization (linked CE-QUAL-W2 and PSO) model develops certain optimal releases (outflow data) from each reservoir outlets in selective withdraw framework during the real time period of spill event. The objective function of simulation-optimization approach in PSRMM is to minimize the reservoir cleanup time and number of downstream water quality standard violation. This paper focuses on the application of PSRMM in a case study of spill scenario involving the release of conservative pollution in Ilam Reservoir. The Ilam Reservoir in Iran is a multipurpose hydraulic project built to provide water for drinking, irrigation, and flood control.