Disposing coal gangue and fly-ash on the surface is a risky method which has tremendous potential catastrophic consequences for the environment, whereas backfill mining is a promising practice turing those hazardous wastes into useful backfill materials. Unfortunately, how to deliver the slurry into avoid efficiently remains underresearched, therefore, to address this gap, in the present paper, in addition to a laboratory rheological test, computational fluid dynamics software Fluent was also employed to simulate the different effects that individual variables have on the pressure evolution at a specific section of the pipeline. Furthermore, the response surface method was implemented to examine how the multiple factors synergistically affect the pressure drop and their corresponding influencing weights. This paper shows that slurry concentration, speed, and pipe diameter all significantly affect the pressure drop of slurry and that conveying speed is the dominant factor in the bend section. In contrast, pipe diameter becomes the dominant factor in the horizontal and vertical pipe sections.