The impact of different diesel-ethanol-methanol-butanol (DEMB) blends on the spray and combustion characteristics of a single-cylinder diesel engine has been investigated. For this study, commercially available software called Diesel-RK that can predict the spray and combustion parameters has been utilized. Some experiments have also been conducted using D100 (100% pure diesel by volume) fuel at a fixed speed of 1500 rpm at peak load while maintaining the same operating conditions as the simulation. The predicted results have been validated against the experimental results obtained with D100. The results of the simulation were found to be in reasonably good agreement with those of the experiment. The analysis of the simulated results shows that the heat release rate, ignition delay and peak cylinder pressure increase for all quaternary blends, whereas the peak combustion temperature decreases at low load and increases at higher load. In terms of spray characteristics, the investigations show that quaternary alcohol blends shorten spray tip penetration (STP) and increase spray cone angle (SCA). Furthermore, as the proportion of ethanol and methanol in the DEMB blends increases, the atomized fuel droplets become smaller in diameter and the sauter mean diameter (SMD) of the blends gradually drops. The authors also suggest that the quaternary blends of this present investigation have a higher potential to be used as a next-generation fuel in diesel engine.