Abstract: The study aimed to use response surface methodology to optimize process parameters for the osmotic dehydration of lettuce under the assistance of ultrasonic. Effect of osmotic agent, sucrose concentration, dehydration time, temperature and ultrasonic power on water loss (WL) and solid gain (SG) was studied.These process conditions were further studied using response surface methodology to maximize water loss and solid gain. The optimal dehydration conditions obtained by response surface analysis were as follows:osmotic dehydration temperature 58℃, osmotic dehydration time 149min, sucrose concentration 42%, and ultrasonic power 200W. Under these optimal dehydration conditions, the water loss and solid gain of lettuce were 1109% and 342.64%, respectively.