Drought stress is considered as a main restriction to have the best potential crops performance in arid and semi-arid regions in the world. Hence, some mechanistic strategies are required to manage drought stress detrimental influences. Silicon as an essential mineral nutrient, plays an important role in physiology, metabolism, and function of crops exposed to drought stress. This study was carried out to evaluate the influences of various irrigation regimes and silicon foliar on three safflower cultivars to find the optimal irrigation level and silicon fertilizer. Three levels of irrigation (0, 2 and 4 times irrigation during growth) were main plots and sub plots were three silicon foliar levels (0, 1 and 2 mM) and three safflower cultivars (Goldasht, Padideh and Golmehr). This experiment was performed in Firouzabad city, Fars Province, Iran with latitude 28°51' N and longitude 52°36' E, during 2018 and 2019. Malondialdehyde content (MDA), polyphenol oxidase (PPO), superoxide dismutase (SOD) and ascorbate peroxidase (APX), oil yield, oil content and seed yield were measured on these cultivars. Interactive effects of irrigation, silicon and cultivars were significant (p<0.01) for MDA, APX, oil yield and oil content. Drought stress in the all safflower cultivars caused a decline in seed yield, oil content and oil yield. On the other hands, silicon was mediated to decrease effect of drought stress and increased amount of seed yield, oil content, oil yield, PPO and SOD. The highest seed and oil yield were observed in Goldasht cultivar under full irrigation and 2mM silicon. Thus, it can be suggested that 1 mM of silicon foliar may ameliorate the performance of safflower exposed to drought stress.