Crude oil desalter effluent from a Tehran oil refinery was treated by a hybrid UF/RO membrane separation process. Ultrafiltration (UF) was used primarily to remove the emulsified oil droplets followed by the removal of total dissolved solids (TDS) via reverse osmosis (RO). The UF membrane was a hydrophilic flat sheet polysulfone ultrafiltration membrane with MWCO of 100 kDa while the RO membrane was a spiral-wound thin-film composite polyamide. Effect of operating conditions such as transmembrane pressure and crossflow velocity were studied in UF pretreatment. The experimental results showed that the UF membrane removed more than 75% of the oil and can be considered as an effective pretreatment. Moreover, RO removed more than 95% of TDS from the desalter effluent. It was concluded that treatment of the desalter effluent using the UF/RO membrane separation process was feasible and desirable.