Silicon nanoparticles have distinctive physicochemical characteristics and are able to enter into plants and impact the metabolism of plants as well as improve plant growth and yield under unfavourable environmental conditions. Besides, low soil organic matter content, imbalanced nutrient and inadequate water supply may adversely affect crop productivity in semiarid areas. To understand the effects of foliar spray of silicon dioxide nanoparticles (nSiO2) with application of farmyard manure (FYM) or inorganic fertilizer on morpho-physiological traits and yield of safflower, a field experiment was carried out in a highland semiarid region of Maragheh, northwest Iran. The experiment consisted of two levels of nSiO2(0 and 20 mM) and four fertilizer regimes (control, 15 t ha−1FYM, 30 t ha−1FYM, 90 kg ha−1N-P-K chemical fertilizer). Safflower plants were treated with nSiO2suspension at leaf development, branching and capitulum emergence stages. Although the nSiO2significantly improved some growth parameters such as canopy spread, stem diameter, plant height, ground cover and the number of achenes in capitulum, it did not affect achene yield and harvest index. However, fertilizer treatments considerably affected most of morpho-physiological traits, achene yield and yield components. The result showed that the best growth and the highest achene yield were achieved by application of 30 t ha−1FYM before sowing. Application of high FYM increased the achene yield by 48% compared to the control, however, application of N-P-K chemical fertilizer or of 15 t ha−1FYM improved achene yield only up to 17% over the no fertilizer condition. Moreover, this work revealed some positive effects of exogenous application of nSiO2on safflower growth. This finding suggests that application of organic fertilizers with foliar spray of nSiO2can improve safflower production and is an advisable agronomic option.