Solar seawater desalination has been gradually developing as one of the most promising desalination processes with renewable energy. In this paper, an indirect solar seawater desalination plant, based on a multi-effect distillation (MED) process and partially powered by a evacuated tube solar collector, was considered. In order to optimize the design parameters, a mathematical model of the plant was developed and a computer simulation program was constructed. A meteorological radiation model was used to estimate the hourly distribution of beam radiation as a function of time (day and hour), locality, and local weather (mainly visibility and humidity). The hourly distillate production of the plant during the daytime was simulated based on the solar radiation model. Analysis was performed as a function of the number of effects, concentration ratio (CR), and operating temperature. Results were presented as the effect on the parameters controlling the unit product cost, which include the specific heat consumption and the specific heat transfer area. Results indicate that the variation trend of the hourly distillate production of the plant during the daytime is almost corresponding to the solar radiation. The specific heat consumption decreases with the increasing of the number of effects, and the change is slowed down gradually. Also, the specific heat consumption rises with the increase of the operating temperature. The specific heat transfer area is strongly related to the number of effects and the operating temperature; it has a rapid growth by raising the number of effects or decreasing the operating temperature. The concentration ratio has a certain influence on both the specific heat consumption and the specific heat transfer area. The analysis performed is helpful not only for selecting the suitable design parameters to increase production, but also for prediction of the performance of existing plants over a wide range of possible operating conditions.