At present, the water productivity have an extremely important in agriculture. In recent years, the use of greenhouses is one of the ways that is concerned to increase the water productivity in agriculture. Soil-less cultivation is one of the new greenhouse cultivation methods that can be effective in increasing efficiency and performance improvement of crops. On the other hand, water is the most important parameter in the crops irrigation management especially in greenhouse crops water consumption. The purpose of this study is to determine the lettuce water consumption and the effect of saline water on its performance. The treatments were performed at the greenhouse soilless culture of Isfahan University in the microlysimeters based on the completely randomized design and eight replications. The treatment consisted of four combination of different cultivation medium (first cultivation medium: coco-peat 50% and perlite 50%; second cultivation medium, coco-peat 90% and perlite 10%; third cultivation medium: perlite 90% and zeolite 10%; fourth cultivation medium: perlite 100%) and two types of water, freshwater (EC=0.48 dS/m) and saline water (EC= 2.5 dS/m). The weight balance method was used for the determination of the water consumption in microlysimeters. During the growing season, meteorological data were measured in the greenhouse. To investigate the water consumption in each of the cultivation mediums, a non-linear regression model was developed to predict the lettuce water consumption in the greenhouse. Also, the effect of meteorological parameters on the water consumption were examined by the regression model. Accuracy of the fitted regression model to predict the lettuce water consumption was desirable in each of the cultivation mediums. The sensitivity of meteorological parameters to predict the amount of water consumption showed that the minimum temperature had the minimum and the solar radiation had the maximum sensitivity of the input parameters on water consumption. Also, the results indicated that the total water consumption in two months growing season, was 294.42 mm (5.44 lit) for the zeolite-perlite cultivation medium, 260.1 mm (4.81 lit) for the coco-peat 50%-perlite 50% cultivation medium, 206.48 mm (3.83 lit) for the coco-peat 90%-perlite 10% cultivation medium and 164.35 mm (3.04 lit) for the perlite 100% cultivation medium. The maximum lettuce water use efficiency, biomass and fresh crop weight were 0.0059 kg m 3 -1, 258.63 gr and 34.79 gr for the zeolite-perlite cultivation medium, respectively. The maximum fresh weight and biomass were 186.17 and 23.07 gr respectively in the case of irrigation with saline water. In this study, the zeolite- perlite cultivation medium was diagnosed as the best cultivation medium for both saline and fresh waters. Based on the obtained results, the regression models can be used to determine the water consumption of crops greenhouse environment. Keywords: Greenhouse, Soil-less Cultivation, Water Consumption, Coco-peat, Lettuce.