The study evaluated the anti-nutrient composition of fluted pumpkin, Telfairia occidentalis Hooker fil. leaf grown in different NPK 20-10-10 hydroponic solutions. The solutions varied in the amount of NPK (20-10-10) granules (25, 50, 75, 100g, 125 and 150 g) dissolved in water containing micronutrients. The growth media were designated as: M25NPK, M50NPK, M75NPK, M100NPK, M125NPK, M150NPK, and Control. Two-week old seedlings of fluted pumpkin raised using River-sand were transferred into the growth media in four replicates. The hydrogen cyanide, oxalate, phytate, tannin, saponin, trypsin-inhibitor, alkaloid, and flavonoids were determined 5 weeks after planting following standard procedures. Waters 616/626 HPLC was used to determine alkaloid and flavonoid contents. The result showed that the proportion of phytochemicals in the leaves among the growth media range thus: phytate (3.445 – 15.837%), tannin (0.729 – 1.974%), oxalate (3.279 – 8.882%), trypsin-inhibitor (1.018 – 2.756%), saponin (6.075 – 7.558%) and hydrogen cyanide (0.014 – 0.020 ppm). Higher values of phytochemical in the leaves were recorded at M100NPK growth media (for tannin, oxalate, saponin and trypsin-inhibitor). The most abundant group of alkaloids present in the leaves was pyridine with percentage occurrence with respect to the total alkaloids across the growth media as thus: 35.72% (Control), 32.36% (M25NPK), 16.80% (M50NPK), 60.83% (M75NPK), 34.68% (M100NPK), 38.69% (M125NPK), and 61.28% (M150NPK). The most abundant flavonoid was luteolin (9.153 g/100g) followed by eriodictyol (7.573 g/100g) at M50NPK medium, while the lowest value (0.004 g/100g) was epicatechin and anthocyanine at M150NPK and M125NPK media, in that order. The study revealed that appropriate proportion of NPK 20-10-10 in solution could be used in growing fluted pumpkin.