Crude oil usually includes water, salty materials, suspended solids, and solvable metal particles. Desalting or dehydration is the first step in the refining process. This process is done to reduce or remove contaminants, corrosion, plugging and fouling of equipment. This paper investigates the effect of four factors (density, freshwater injection, heating, and mixing) on the efficiency of the dehydration/desalting process for Iranian crude oil and a commercial demulsifier (PETRO 1020 BA). These factors are systematically varied, and efficiency is analyzed. Two efficiencies are defined: a Salt Removal (S/R) efficiency and a Water Cut (W/C) dehydration efficiency. Statistical analysis of Plackett–Burman (P-B) along with response surface methodology (RSM) was used in the optimization process. The results showed that the high density of crude oil affects desalting/dehydration process adversely. Furthermore, it suggested that heating is the most important factor that improves efficiencies of S/R and W/C. The highest efficiencies were obtained at heating of 120˚C. The result of this research shows that the mentioned model has good agreement with experimental data.