A new type of continuous harvester is designed to address the problems of high labor cost and low efficiency in the process of harvesting lettuce in greenhouse hydroponics. The designed harvester is mainly composed of three parts, namely, reciprocating cutter, driving mechanism, and belt conveyor. The response surface method is used to establish the mathematical model between the force acting on the lettuce roots and the reciprocating speed of the cutter, the inclination angle of the cutter, and the conveying speed of lettuce. The reliability of the mathematical model is verified, and the optimal parameter combination of the force on the lettuce root is obtained. Considering the actual harvesting method, the destruction rate, damage rate, and success rate of lettuce are used as the design indexes in the experiment. Results showed that the force on the lettuce stem is the smallest under the optimal parameter combination of the reciprocating motion speed of the cutting blade (100 mm/s), the inclination angle of the cutting blade (2.31°), and the conveying speed of the lettuce (64.49 mm/s). When the minimum force is 1.91 N, the destruction rate of lettuce harvest is 1.85%, the damage rate of lettuce is 3.71%, and the success rate of lettuce harvest is 94.44%. This study offers a potential solution for the automatic harvesting of hydroponic lettuce in a greenhouse.