A design of experiments was evaluated in optimizing MOF-5 synthesis for acetylene adsorption. At first, mixture design was used to optimize precursor concentration, terephthalic acid, zinc acetate dihydrate and N,Ndimethylformamide. More specifically, 13 conditions with various molar ratios were designed by extreme vertices design method. After preparing the samples, XRD, N2 physisorption and SEM analysis were performed for their characterization. Moreover, acetylene adsorption experiments were carried out over the samples under identical conditions. The optimal precursor composition for MOF-5 synthesis was predicted on a molar basis as follows: terephthalic acid : acetate dihydrate : dimethylformamide = 0.1 : 0.4 : 0.5. Thereafter, multi-level factorial design was designated to investigate the effect of synthesis reaction conditions such as temperature, time and stirring speed. By the statistical analysis of 18 samples designed, 4 reaction parameters were determined for additional adsorption experiments. Therefore, MOF-5 prepared under the synthesis time and temperature of 100 ℃ and 12 h, respectively, showed the maximum adsorption capacity of 15.1 mmol/g.