Lettuce is an important vegetable in the human diet and is commonly consumed for salad. It is a source of vitamin A, which plays a vital role in human health. Improvements in lettuce production will be needed to ensure a stable and economically available supply in the future. The influence of nitrogen (N), phosphorus (P), and potassium (K) compounds on the growth dynamics of four hydroponically grown lettuce (Lactuca sativa L.) cultivars (Black Seeded Simpson, Parris Island, Rex RZ, and Tacitus) in tubs and in a nutrient film technique (NFT) system were studied. Hyperspectral images (HSI) were captured at plant harvest. Models developed from the HSI data were used to estimate nutrient levels of leaf tissues by employing principal component analysis (PCA), partial least squares regression (PLSR), multivariate regression, and variable importance projection (VIP) methods. The optimal wavebands were found in six regions, including 390.57-438.02, 497-550, 551-600, 681.34-774, 802-821, and 822-838 nm for tub-grown lettuces and four regions, namely 390.57-438.02, 497-550, 551-600, and 681.34-774 nm for NFT-system-grown lettuces. These fitted models' levels showed high accuracy (R-2=0.85-0.99) in estimating the growth dynamics of the studied lettuce cultivars in terms of nutrient content. HSI data of the lettuce leaves and applied N solutions demonstrated a direct positive correlation with an accuracy of 0.82-0.99 for blue and green regions in 400-575 nm wavebands. The results proved that, in most of the tested multivariate regression models, HSI data of freshly cut leaves correlated well with laboratory-measured data.