In this paper, a three-dimensional Eulerian Lagrangian model is established to perform the full-loop simulation of the combustion process of municipal solid waste (MSW) and coal in an industrial-scale circulating fluidized bed (CFB) boiler. On the basis of the multiphase particle-in-cell (MP-PIC) scheme, the gas phase is modeled by a large eddy simulation (LES) approach and the solid phase by discrete particle method. A comprehensive reaction model including devolatilization, combustion of char and volatiles, formation and retention of acid gas, and production and reduction of NO and N2O is incorporated into the scheme. The simulated CFB boiler consists of the chamber, cyclone, loop-seal, external heat exchanger (EHE), and diplegs. The full-loop gas-solid flow behavior and combustion characteristics are obtained. Numerical results reveal that a fast fluidization regime takes place in the chamber region, while a bubbling fluidization regime appears in the EHE. Serious wall erosion takes place in the horizontal flue duct and the entrance region of the cyclone. The temperature profile is relatively uniform in the whole boiler, and the gas composition profiles show that CO2 concentration is almost opposite to O-2 distribution throughout the boiler. The effects of fuel components and air staging on gaseous pollutant emissions (NO, N2O, SO2, CO, and HCl) are also investigated. The results indicate that the emissions of NO and N2O decrease while the SO2 emission increases with the increasing coal mass share. The increase of secondary air ratio can effectively reduce the NOx emission, but there is no distinct tendency for the SO2 emission.