Foam fractionation is one of the low operating-cost techniques for removing proteins from a dilute solution. The initial bulk solution pH and air superficial velocity play an important role in the foam-fractionation process. Denaturation of proteins (enzymes) can occur, however, during the foam-fractionation process from the shear forces resulting from bursting air bubbles. At the extreme bulk solution pHs (lower than 3.0 and higher than 10.0), the enzymatic activity of cellulase in the foamate phase drops significantly. Within these two pH bounds an increase in the air superficial velocity, V-0, and a decrease in the bulk solution pH leads to a decrease in the separation ratio (SR), defined as the ratio of the protein concentration in the foamate to the protein concentration in the residue. On the other hand, an increase in V-0 provides a higher foamate-protein recovery. The process efficiency is defined as the product of foamate-protein recovery times the SR times the cellulase activity. The optimal operating condition of the cellulase foam-fractionation process is taken into account at the maximum value of the process efficiency. In this study, that optimal condition is at an air superficial velocity of 32 cm/min and a bulk-solution pH of 10.0. At this condition, the recovered foamate is about 80% of the original protein mass, the SR is about 12, and the enzymatic activity is about 60% of the original cellulase activity.