The effects of the important flotation parameters on the cleaning process of the Himmetoglu oil shale from Turkey were investigated. The individual and multiple interaction effects of conditioning time, flotation time, pulp density, particle size, and frother dosage were determined using statistical analysis and factorial design of experiments. The influence of these parameters on the cleaning performance were evaluated in terms of ash yield, calorific value, and combustible recovery of the concentrates. XRD studies were also carried out to view the variations in the organic and inorganic content of the concentrates. Optimum parameter conditions, which provided the most effective cleaning, were determined by the applied model. It was seen that all parameters affected the flotation performance with varying degrees of significance. At optimum conditions, flotation performance increased and the ash yield of the concentrate decreased to 16.81% with 84.10% combustible recovery, and the calorific value increased to 5564.02 kcal/kg. XRD spectra revealed that the extent of mineral matter removal depended on the flotation performance, and the inorganic matter was effectively removed at optimum conditions.