The mechanized harvesting of lily fruit in Southern China is affected by a high damage rate of lily fruit and low rate of soil breakage. The existing fruit–soil separation device is not suitable for heavy soil in Southern China. This study aimed to design a flexible fruit–soil separation device that can effectively reduce the damage rate of lily and improve the crushing rate of the soil. Thus, it would meet the requirements of southern lily fruit harvesting. In this study, the soil breaking rate and lily damage rate in the fruit–soil separation were taken as the assessment indexes, and the linear speed of the front conveyor belt, the inclination angle and the rotating speed of the fruit–soil separation device were recognized as the test factors. By performing the Box–Behnken test, three-factor and three-level experimental research on the fruit–soil separation device of the lily harvester was conducted. On this basis, a multiple regression model of the assessment indexes to the respective was built, the effect of various factors on the operation quality was analyzed and optimal operation parameters were determined. When the optimal parameter was adopted in the test (e.g., the linear speed of the front conveyor belt, the inclination angle and the speed of the fruit–soil separation device reaching 1.2 m·s−1, 36° and 98 r·min−1, respectively), the soil crushing rate was 92.8% and the lily damage rate reached 8.9%, and the fruit–soil separation effect satisfied the requirements of lily fruit harvest. The results could be referenced for other subsoil fruit harvesters and fruit–soil separation devices under heavy clay soil in Southern China.