Safflower (Carthamus tinctorius L.) is a multipurpose plant; since its seeds contain multi-saturated fatty acids it is grown as an oilseed plant. Drought stress at late season, reduces both seed yield and quality. On the other hand, the use of nanoparticles due to their high contact surfaces can reduce the effects of environmental stresses. Hence, the present study was carried out to investigate the effects of Nano-silicon oxide (10 and 20 mM), Nano-titanium dioxide (25 and 50 mM) and Nano-zinc (30 and 60 mM) on the growth and yield of spring safflower exposed to different moisture regimes (non-stress, drought stress, and severe stress) in 2015. The results of this study showed that the application of nanoparticles decreases the negative effects of drought stress. Among nanoparticles, the application of nano-titanium improved the amount of chlorophyll index, concentration of protein, ash and oil, moisture content, α-amylase activity and canopy temperatures by 11.45, 28.68, 15.47, 14, 38.02, 16.38 and 16.71 percent, respectively. The highest amounts of linoleic and oleic fatty acids were observed in 50 mM nano-titanium treatments and non-application of nanoparticles under drought stress conditions. It can be concluded that application of nanoparticles, especially nano-titanium, may have a positive effect on reducing the effects of drought stress and improve the quality and quantity of safflower seed oil.