The present work deals with application of 25-2 fractional factorial design (FFD) to evaluate the operating parameters on starch separation from synthetic starchy wastewater using a hydrophilic polyethersulfone membrane with 0.65 μm pore size in a plate and frame handmade membrane module. The analysis of variance (ANOVA) combined with F-test was also used to recognize non-significant terms. The performance of the filtration process was evaluated by calculating the COD removal percentage (rejection factor) and permeate flux. In this experiment, five input parameters were surveyed, including trans membrane pressure (TMP), flow and temperature of feed, pH and concentration of wastewater. In this experiment, real wastewater was not used but synthetic starchy wastewater was prepared using starch. Two models were obtained from experimental data, capable of predicting COD removal percentage and permeate flux in different conditions. The predicted values obtained from the regression models were close to the actual ones. For the reduction of fouling, cleaning in place (CIP) method was used.