Droplet size distribution (DSD) of an emulsion is one of the important properties that affect product quality, stability, appearance, and rheology. Reliable prediction of DSDs in high-pressure homogenizers under various emulsion formulation and processing conditions is still challenging. A zero-dimensional population balance equation (PBE) model was developed to take account of the heterogeneous turbulent dissipation rate through its volume fraction distribution rather than the mean value as the coupling parameter between CFD and PBE. Furthermore, the effect of emulsifier on coalescence was also incorporated through the surface coverage of emulsifier. The model can give satisfactory DSDs under different oil fractions, homogenization pressures, and emulsifier concentrations for the oil-in-water emulsions. Moreover, the predictions were more sensitive to the breakage kernel parameters than to the coalescence ones or the number of daughter droplets. This approach is beneficial to the fast computational product design with less computational cost and reasonable prediction.