Abstract: The optimization of semi-batch esterification of higher fatty acid by methanol is studied by choosing production cost as objective function, methanol feed flux as control variable and reaction pressure as control parameter. Dynamic programming and Powell methods are separately used to solve this problem, and the calculated results are consistent. Calculation shows that optimal operation will reduce the production cost by 5 to 15 percent and higher profit will be gained in the case of catalytic esterification process. The effects of methanol price and operation cost on optimal operation strategies are discussed. The amount of calculation work by using two different methods of solution are compared. It is proved by experiments that the proposed optimal operation strategy as well as its goal can be achieved.