This investigation was conducted during the two winter seasons of 2017 and 2018 to study the effect of soil application of nano NPK at rates of (0, 12.5, 25, 50 %) from the recommended dose of conventional NPK chemical fertilizers on growth, yield, and head quality of lettuce. The results showed that the high rate of nano nitrogen (50%) significantly increased the vegetative growth expressed as plant fresh weight, leaf area head fresh weight, head size, firmness, total yield and marketable yield. Moreover 50 % of nano potassium treatment produced the highest significant increment of ascorbic acid, TSS and head total sugars content. However, the highest significant total chlorophyll, carotenoids and dry matter content was recorded with nano nitrogen (50%), while head phosphorus, and potassium content were reached the highest values with 50% nano phosphorus and nano potassium respectively. Head nitrate content significantly increased with control NPK conventional over all nano treatments. It was concluded that vegetative growth, yield and marketable yield responded positively to the application of 50% nano nitrogen while head quality significantly increased with 50% nano potassium fertilization.