Abstarct: Water stress is one of the most important factors limiting the growth and production of crops in most parts of the world. Seed priming is one of the effective methods to stand with this stress and improve the performance. In order to study the effect of seed priming with salicylic acid on yield, physiological and biochemical indices of safflower cultivars under water deficit conditions an experiment was conducted as split plot factorial baxsed on randomized complete block design with three replications at Shahrood Agricultural and Natural Resources Research and Education Center for two years (2015 and 2016). The main plot consisted of irrigation at three levels baxsed on the evaporation from class A evaporation pan including non water stress (Irrigation after 60 mm evaporation), mild water stress (Irrigation after 120 mm evaporation) and severe water stress (Irrigation after 180 mm evaporation) and subplots consisted of combination of two factors include safflower cultivars (Goldasht, Sina and Soffeh) and seed priming (Treated seeds with salicylic acid 1.5 mM for six hours and non treated seeds). Results of combined data analysis showed that significant increase in grain yield and its components in priming treatment compared to control plots in each two years of the experiment. Goldschat cultivar had the highest chlorophyll content under non-stress conditions and mild water stress, resulting in high yield and yield components So that the highest grain yield was obtained 3800 kg ha-1 in Goldasht cultivar primed with salicylic acid under non-stressed conditions. In water stress conditions, activity of superoxide dismutase, peroxidase, ascorbate peroxidase and catalase enzymes was increased about 29, 26, 25 and 43 percent respectively. In this condition, content of malondialdehyde, proline, carotenoid and grain protein significantly increased but the other traits such as yield and yield components, biomass, harvest index and grain oil content were decreased. baxsed on the results of experiment, seed priming with salicylic acid, increased about 8, 6, 5 and 11%, respectively, the activity of superoxide dismutase, peroxidase, ascorbate peroxidase and catalase enzymes, caused increasing the grain yield under stress conditions and plant resistance to water stress. In this study, the percentage of oil and protein were significantly affected by water stress, with increasing in the intensity of the stress, the percentage of oil decreased and protein content increased. The results showed that the maximum oil yield of 1178 kg ha-1 obtained from soffeh cultivar primed with salicylic acid under non-stress condition in the second year of experiment. Interaction effects of year with irrigation and cultivars appeared to be significant on 1000 grain weight, grain yield, biological yield, oil yield and activity of superoxide dismutase, peroxidase and ascorbate peroxidase enzymes. So that the most 1000-weight and biomass weight obtained from Goldasht cultivar under non-stress conditions in the second year of experiment.