311-A best regression design of supposed saturation and {3, 3} saturated design of single barycenter check were used to study the effects of NPK application rates and N application proportion in different growing periods on lettuce economical yield, fertilization profit. The results showed that the best NPK application of lettuce with maximum economical yield of 41.859t/hm2 was N90.92kg/hm2, P2O566.38kg/hm2 and K2O 116.84kg/hm2, the best NPK application with the best fertilization profit of 26822.78 yuan/hm2 and economical yield of 41.849t/hm2 was N94.31kg/hm2, P2O565.97kg/hm2 and K2O116.48kg/hm2, and better N application proportion of basal manure, former and latter topdressing with higher expecting economical yield of 45.340t/hm2 was 0.402:0.328:0.270,three periods N application quantities were N37.79kg/hm2, 30.83kg/hm2 and 25.38kg/hm2, respectively.