The present research has been conducted with the aim of investigating the effect of zeolite on two varieties of lettuce (Lactuca sativa) under salinity stress conditions. The experiment was performed with a factorial method which included three factors of zeolite, salinity and variety (Shushan and Taftan) in a completely randomize design. Salinity stress was applied in four concentrations of 0, 25, 50, and 75 mM of NaCl along with nutrient solution. Zeolite was mixed with cocopite and perlite at different levels of 0, 5, 10, and 15% (V/V). The results indicated that salinity stress leads into a decrease in lettuce yield. Use of zeolite in the substrate caused a decrease negative effect of salinity so that the maximum of lettuce yield was related to 10% zeolite treatment and with no salinity stress in Taftan variety.