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Article type: Research Full Paper Seed osmopriming is an effective strategy to improve the germination process. Screening and estimating the optimal concentrations of different osmotic compounds is the first step in seed osmopriming. In this study, the effects of treatment with single osmotic compounds were initially evaluated at different concentrations, namely NaCl (0, 1, 2, 3, 4, 5, 10, 20, 30 g/l), ZnSO4 (0, 1, 5, 10, 20, 30 and 40 mM), proline (0, 1, 5, 10, 20, 30 and 40 mM), and trehalose (0, 1, 5, 10, 20, 30 and 40 mM) on wheat seeds. Then, the surface-response method was designed in the form of a Box-Benken design. Results showed a significant increase in wheat seed germination at concentrations of 3 and 10 g/l NaCl, 1 and 20 mM ZnSO4, 1 and 10 mM proline, and 0 and 1 mM trehalose. These concentrations were validated using the surface-response method and experiments. The values of coefficient of determination (R2= 0.99) and adjusted R2 (R2adj= 0.99) showed that the obtained model is suitable for data analysis. One-way analysis of variance confirmed the quadratic model as the best model to determine the interaction of the studied variables (P< 0.0001). The optimal values were proposed as a combination of 3 g/l NaCl, 1 mM ZnSO4, and 1 mM proline. In another experiment, using the values predicted by the model, it was found that the surface-response method can be used in screening and germination optimization tests. The results of the follow up experiment using the values determined in the model revealed that the surface-response method can be considered in screening and optimization studies of seed germination.