This study was performed to evaluation of interaction of silicon application and irrigation on agronomic and physiologic traits of safflower at 2018 and 2019. The experiment was conducted as a split plot factorial based on randomized complete block design with 3 replications. The irrigation was main factor (0, 2 and 4 times during growth) and the sub-factor were silicon foliar application (at three levels: 0, 1 and 2 mM) and three safflower cultivars (Goldasht, Padideh and Golmehr). The studied traits were: number of seeds per boll and 1000-grain weight, number and weight of boll, number of lateral branches and branch diameter, plant weight and total plant weight, floret yield, grain yield, chlorophyll a and b, proline and antioxidant enzymes. According to results, treatments had significant effects on studied traits at 5 or 1% statistically level. 2 and 3 times irrigation led to 7 and 24% the increasing of seed yield in compare to control, respectively. It was obtained that 1 and 2mM silicon led to 25 and 15% the increase of seed yield in compare to control. Interaction between treatments showed that the highest seed yield (500g per m2) was observed by Goldasht cultivar under 4-time irrigation and 2mM silicon. Therefore, it can be suggested that Goldasht with 2 mM silicon be used to reduce the effects of dehydration.