An orthogonal array design (OA 32 ) was employed as a statistical optimization method to enhance the performance of the synthesis of 2,4,6,8,10,4,6,8,10,. The current application of the Taguchi method was successful in optimizing the experimental parameters of HNIW synthesis. High-purity HNIW was synthesized on a relativity large scale by the one-pot method using addition of N 2 O 4 , HNO 3 , and H 2 SO 4 to tetraacetyldibenzylhexaazaisowurtzitane (TADB). The effects of reaction conditions such as the TADB:N 2 O 4 , N 2 O 4 :HNO 3 , and HNO 3 :H 2 SO 4 ratio, the temperature of nitrosation, the temperature of addition of HNO 3 and addition of H 2 SO 4 , the time of nitrosation, and the time of addition of HNO 3 and H 2 SO 4 on the yield of synthesized HNIW were investigated. The effects of these factors on the yield of HNIW were quantitavely evaluated by the analysis of variance (ANOVA). The results showed that the yield of HNIW synthesis can be enhanced significantly by controlling the temperature of addition of H 2 SO 4 and the time of nitrosation. Finally, optimal conditions for synthesis of HNIW by the one-pot method were proposed. The results of ANOVA showed that the optimal TADB:N 2 O 4 , N 2 O 4 :HNO 3 , and HNO 3 : H 2 SO 4 ratios are 6, 1:2, and 1:1, respectively; also, the optimal temperatures for nitrosation, addition of HNO 3 , and addition of H 2 SO 4 are 60, 20, and 60 °C, respectively, and the optimal times for nitrosation, addition of HNO 3 , and addition of H 2 SO 4 are 10, 0.5, and 2.5 h, respectively, for producing HNIW. Finally, under optimal conditions, the yield of the reaction is ∼96%.