To provide production basis for high yield of pumpkin seeds, the authors used quadratic regression orthogonal rotary combination to set tests of four factors and five levels, and studied the effects of NPK combined fertilization and rational close planting on seed yield of pumpkin. The results showed that different amounts of four measures had comprehensive and significant effect on pumpkin yield, single factor measure and seed yield presented an unitary quadratic parabola relationship, the interaction effect of nitrogen, phosphate, nitrogen, and density on seed yield of pumpkin reached significant level, namely, the yieldimproving effect of one of the two factors and the other factor had significant differences between different levels. Comprehensive analysis showed that: under this experimental condition, the best treatment was nitrogen fertilizer of 223-249 kg/hm2, phosphate fertilizer of 152-174 kg/hm2, potash fertilizer of 164-168 kg/hm2 and planting density of 39391-40456 strain /hm2.