Abstract: In order to explore the high-yield and high-efficiency fertilizer and density cultivation scheme of Quandou 20 and accelerate the popularization and application of varieties, a four-factor (full implementation) with five-level quadratic general rotation combination design was used to study the effects of density (X₁), nitrogen fertilizer (X₂), phosphorus fertilizer (X₃) and potassium fertilizer (X₄) on the yield of Quandou 20. Then, the second-order regression mathematical model with the yield of Quandou 20 as the objective function was established, and the main effects and interaction effects of each factor on the yield were analyzed. The results showed that the second-order regression mathematical model established by the experiment reached a very significant level, and the regression model had a good fit with the actual situation. The significance test results of regression coefficient showed that the first order term of planting density was significant level, and the second order term was extremely significant level. The quadratic terms of nitrogen fertilizer, phosphorus fertilizer and potassium fertilizer were all extremely significant; the interaction effect of phosphate fertilizer and potassium fertilizer was significant. The order of influence of each factor on the yield of Quandou 20 was as follows: potassium fertilizer > density > nitrogen fertilizer > phosphorus fertilizer. According to the model, the cultivation methods of Quandou 20 with the yield more than 2270.07 kg·hm⁻² were determined as follows: planting density of 243 100-262 300 plants·hm⁻², nitrogen fertilizer of 78.42-91.59 kg·hm⁻², phosphorus fertilizer of 252.60-311.10 kg·hm⁻², potassium fertilizer of 81.96-93.51 kg·hm⁻².