Foxtail millet (Setaria italica (L.) Beauv.) is an economically and nutritionally important crop grown primarily in Asian countries. However, optimal NPK fertilizer application rates and ratios have not been established for foxtail millet cultivation. In this study, a two years field experiment was conducted in typical warm-temperate sub-humid continental monsoon climate of brown soil, aimed to establish a rational nitrogen:phosphorus: potassium (N:P:K) ratio to improve foxtail millet production. Four N (0, 112.5, 225.0, and 337.5 kg ha-1), four P (0, 45.0, 90.0, and 135.0 kg ha-1), and four K (0, 75.0, 150.0, and 225.0 kg ha-1) fertilization rates were employed in fourteen different treatments. Crop yield, agronomic characteristics, and nutrient enrichment were evaluated. Crop yield was significantly influenced by the N:P:K ratio. The highest crop yield (3927.0 kg ha-1) was achieved with 112.5 kg ha-1 N, 90.0 kg ha-1 P, and 150.0 kg ha-1 K treatment. It was 68.8% higher than the control. The optimal N, P, and K application rates were 130.4-173.5, 83.5-103.8, and 133.4-153.2 kg ha-1, respectively. Crop yield was positively correlated with plant height, leaf length and width, kernel P and K, and chlorophyll. Rational fertilization improves foxtail millet yield and may be applied for the improvement of crop productivity and the mitigation of agricultural pollution. [ABSTRACT FROM AUTHOR]