Abstract: Foxtail millet (Setaria italica L.) is of high nutritious value, which has been mostly used for foods in Africa, Asia and Central and South America. To investigate the effects of fertilization and density on photosynthetic characteristics and yield of millet, Zhangzagu 5, an experiment based on quadratic general rotary unitized design with 3 replications was conducted. The results show that the yield is significantly positively correlated with leaf area index, net photosynthetic rate and chlorophyll content (SPAD). The levels of nitrogen, phosphate and potassium and the row spacing all have significant effects on the net photosynthetic rate and yield of millet, and the net photosynthetic rate and yield are mainly affected by the nitrogen level and row spacing, while the influence of phosphate and potassium are relatively small. The row spacing, plant spacing and nitrogen level have great effects on leaf area index, and leaf area index is increased at first and then decreased with the increase of N level and decreases of row spacing or plant spacing. The effects of nitrogen and potassium levels on chlorophyll contents are obvious, and the chlorophyll contents have a trend from rising to declining with nitrogen or phosphate increasing. The interactions between the nitrogen level and potassium level and plant spacing, and the interaction between the potassium level and plant spacing show significant effects on yield, and the interactions between the nitrogen level and potassium level and plant spacing show great effects on net photosynthetic rate. The interaction effects of other factors on photosynthetic characteristics and yield are not obvious. Multivariate quadratic regression analysis indicates that the regression relationship between the levels of nitrogen, phosphate and potassium, row spacing, plant spacing and the yield of Zhangzagu 5, can be used for production forecasts. The recommended cultivation conditions for Zhangzagu 5 are 178-197 kg/ha for nitrogen level, 88-101 kg/ha for P2O5, 54-67 kg/ha for K2O, 22-24 cm for row spacing, and 12-13 cm for plant spacing. These results suggest that nitrogen, phosphate and potassium, row spacing, plant spacing and their interactions have certain effects on the leaf area index, net photosynthetic rate and chlorophyll content (SPAD) and yield of Zhangzagu 5. The research lays a theoretical foundation for reaching high and stable millet yield and spreading hybrid millet to a large area.