High yield and quality of lettuce were objects under the intercropping aeroponics system with cherry radishes. The orthogonal test of three factors and three levels were enforced to reduce nitrate content in edible parts of lettuce under the intercropping aeroponics system. According to a large number of single factor experiments in previous researches, the orthogonal test was utilized to study the influence of intercropping ratio, phased management of nutrient solution concentration and the time of preharvest light supplementation on target plants. The results showed that the optimal combination of factors in the cultivation management mode was as follows: the intercropping ratio of lettuce and cherry radish was 2; the nutrient solution was supplied by 0.5 standard concentration in the early stage and in the week before harvest in stages, and standard concentration in the middle stage; and the time of preharvest light supplementation was 48h. High yield, high quality and low nitrate content in the edible parts were found for lettuce in optimal cultivation management mode, which meant that the optimization was obvious. That’s to say, the cultivation management mode provided theoretical basis and reference for the study of soilless cultivation of high quality leafy vegetables with low nitrate.